docent/ShutterstockWhether or not theres a scientific benefit to being baldwell let the follically challenged among us be the judge of thatscientists continue to search for a balding cure. According to UCLA researchers, that isnt completely out of the question. A team, led by Heather Christofk, PhD, and William Lowry, PhD, found a new way to activate the stem cells in the hair follicle to make hair grow. Their findings, published in the journal Nature Cell Biology, may lead to new drugs to promote hair growth or work as a cure for baldness or alopecia (hair loss linked to factors like hormonal imbalance, stress, aging or chemotherapy).

Working at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, the researchers discovered that the metabolism of the stem cells embedded in hair follicles is different from the metabolism of other cells of the skin. When they altered that metabolic pathway in mice, they discovered they could either stop hair growth, or make hair grow rapidly. They did this by first blocking, then increasing, the production of a metabolitelactategenetically.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, says Dr. Lowry, a professor of molecular, cell and developmental biology, as reported on ScienceDaily. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

Two drugs in particularknown by the generic designations of RCGD423 and UK5099influenced hair follicle stem cells in distinct ways to promote lactate production. The use of both drugs to promote hair growth are covered by provisional patent applications. However, they are experimental drugs and have been used in preclinical tests only. They wont be ready for prime time until theyve been tested in humans and approved by the Food and Drug Administration as safe and effective. (While youre waiting for a male pattern baldness cure, check out these natural remedies for hair loss.)

So while it may be some time before these drugs are availableif everto treat baldless or alopecia, researchers are optimistic about the future. Through this study, we gained a lot of interesting insight into new ways to activate stem cells, says Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

This 7-year-old girl living with alopecia will inspire you.

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This New, Cutting-Edge Treatment Could Be the End of Baldness - Reader's Digest

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MIAMI, Sept. 6, 2017 /PRNewswire/ --Longeveron LLC, a regenerative medicine company developing cellular therapies, announced today that it treated its first patient in the Company's Phase 2b clinical trial evaluating the safety and efficacy of Longeveron human Allogeneic Mesenchymal Stem Cells (LMSCs) in patients with Aging Frailty Syndrome. This trial is being conducted pursuant to an Investigational New Drug Application (IND) in conformance with U.S. Food & Drug Administration (FDA) regulations. Aging Frailty is a common geriatric medical condition that is serious and life-threatening, and for which there are currently no U.S. Food and Drug Administration-approved therapeutics available.

The clinical trial is designed to enroll 120 subjects from approximately 10 medical centers around the U.S. The primary objective of the study is to evaluate the effect that LMSCs have on functional mobility and exercise tolerance in elderly Aging Frailty subjects. Three different LMSC dose groups will be compared to placebo over 12 months in a randomized, double-blinded, parallel arm design.Specifically, the trial will evaluate changes to the following:

"Frailty Syndrome is a very common and difficult situation to manage from a clinician's and caregiver's standpoint," stated Marco Pahor, M.D., Director of the Institute on Aging at the University of Florida. "The goal of intervention is to stop or slow the progression towards dependence and adverse health outcomes common to the syndrome, and to restore the patient to a state of healthy aging and functional independence. Longeveron's regenerative medicine trial is an important step towards the development of an effective therapeutic."

Allogeneic mesenchymal stem cells (MSCs) were previously tested in a Phase I/2 proof-of-concept study conducted by investigators at the University of Miami'sMiller School of Medicine. In that study, MSCs were shown to be safe and well-tolerated in frail, elderly subjects in a Phase 1 open label single ascending dose trial (publication link here) with a similar safety profile observed in the randomized, placebo-controlled Phase 2 study (publication link here) Subjects treated with a dose of 100 million MSCs showed significant improvements in six minute walking distance, and significant decreases in systemic inflammation, both relative to baseline.

"As individuals age, stem cell production and proliferation decreases, systemic inflammation increases, and a person's ability to repair and regenerate worn out or damaged tissue diminishes," remarked Suzanne Liv Page, Longeveron Chief Operating Officer. "In frail individuals this is particularly problematic. Our hypothesis is that exogenously infused allogeneic mesenchymal stem cells that are derived from the bone marrow of a healthy young donor, and culture expanded in our lab, will have potent regenerative and restorative effects."

Participants in this study must be between the ages of 70 and 85, be diagnosed as mildly to moderately frail due primarily to aging, and be able to walk between 200 and 400 meters over six minutes. Detailed information about the trial, subject eligibility and participating centers can be found by clicking here or by visiting the website http://www.clinicaltrials.gov and entering trial ID: NCT03169231.

About LMSCs

LMSCs is an allogeneic product, which means it is produced from stem cells derived from human donor bone marrow, and not from the patient's own stem cells, (referred to as autologous). LMSCs are manufactured at Longeveron's Cell Processing Facility in Miami, Fl. using a proprietary ex vivo culture expansion process.

About Longeveron

Longeveron is a regenerative medicine therapy company founded in 2014. Longeveron's goal is to provide the first of its kind biological solution for aging-related diseases, and is dedicated to developing safe cell-based therapeutics to revolutionize the aging process and improve quality of life. The company's research focus areas include Alzheimer's disease, Aging Frailty and the Metabolic Syndrome. Longeveron produces LMSCs in its own state-of-the-art cGMP cell processing facility. http://www.longeveron.com

Contact:Suzanne Liv Pagerel="nofollow">spage@longeveron.com305.909.0850

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Grief is a personal matter.Each of us has our own mechanisms to copethere is no format set in stone, there are no boundaries. For me, the week leading up to my son Arjan Vir's birthday has always been the most difficult to deal with.

I am overwhelmed by a well of emotions: On the one hand, there are all those happy memories, so much excitement building up to planning those wonderful birthday parties themes to be decided, lists to be made, cards to be distributed, menus, games and oh, the return gifts one mustn't forget and then this sudden feeling of hollowness, the sinking depths of which words cannot describe.

Beyond words

I lost my 26-year-old son Arjan Vir to Leukaemia in 2012. Arjan was one of those hugely social people with an enviable optimism about him he loved to have people around him and had the enormous ability to attract people, make friends and share his life with them. His friendships were deeply honest and truly meaningful, there was nothing hollow about them. Those around Arjan loved his happy-go-lucky nature and his laidback attitude towards life.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other. Photo:Simi Singh

My son never lost his ability to make friends despite the battle he was fighting with cancer. Arjan had a battalion of friends in the hospital: ward boys, nurses, lab technicians and resident doctors could be seen about his room whenever they had spare time; some asking for advice on which phone to buy, to have the odd computer issue sorted, if nothing else, just to watch him play computer games.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other.

An intensely sensitive child, Arjan worried more about others than himself he was an avid reader, wrote beautiful poetry and had an imagination that went beyond words.

His passion for computer games had pre-determined his career options, he had decided to study computer graphics and 3D computer animation. Even at the hospital, as he underwent treacherous rounds of chemotherapy, cycle after cycle, his imagination worked overtime planning some game or the other based on his treatment.

Knowing BMT

A Leukaemia patient, Arjan needed a bone marrow transplant (BMT). In a layperson's terms, BMT means that the unhealthy bone marrow is killed under highly sanitised conditions by giving the patient very high doses of chemotherapy and radiation and replaced by a healthy bone marrow. That sounds perfectly simple, but bone marrow transplant remains a complicated and dangerous procedure.

What consequences does that come with?

For the uninitiated, bone marrow is the soft tissue where all our vital blood components RBCs, WBCs, platelets, plasma and stem cells are formed. Killing one's bone marrow essentially means there is no immunity left to take care of our body.

Where does the healthy bone marrow come from if we are to attempt to rid the body of cancer?

There are two broad types of BMT: Autologous where the unhealthy bone marrow from our body is removed, worked upon or mutated and replaced, and the allogenic transplant in which another person's healthy bone marrow replaces our own.

With the second type of transplant come incredible complications and the daunting task of finding the donor bone marrow that must replace ours: one needs to find another person whose DNA is identical to ours. The first and most obvious choice, of course, would be a sibling.

However, the chances of finding the identical DNA HLA typing that matches your siblings' is only 1:4, and if such a match isn't possible, where do we go?

In Arjan's case, our younger son's HLA typing did not match, and the chances of finding an unrelated donor match were one in a million.

This was the worst possible news we could get, worse than the news of Arjan being diagnosed with Leukaemia.

How does one find an identical HLA typing match in this whole world where do you start, whom do you turn to?

[Photo: Weill Cornell Medecine]

Discovering stem cell registry

In 2012, there were no substantial HLA typing registries in India unlike in developed countries, which maintain nationwide registries that are linked to the worldwide bone marrow registry.

The doctors guided us to approach All India Institute of Medical Sciences (AIIMS) while AIIMS did not have a significant registry of its own, it had a membership with the World Marrow Donors Association (WMDA), and hence could do a worldwide search to find an HLA match for Arjan.

However, institutes likeAIIMS have become desensitised to the urgency that such cases demand and we got no response from them.

At the time, Datri in Chennai was the sole functioning stem cell registry it had about 12,000 donors in its data bank, but we did not get a quick response from them either.

Our son's doctors here told us that we were sitting on a "time bomb" we needed to act swiftly, we could lose no time and that's when we decided to take Arjan to the US for his further treatment and then, hopefully, a BMT.

Arjan was distressed to discover the situation in India; when he heard about the lack of registries, his first thought was that once he had recovered, he would set up a meaningful registry at home. His biggest concern was: What do the poor do, where do they go?

And so, five years on, the Arjan Vir Foundation was set up in the memory of our very dear son. Our aim is to run a widespread registry that addresses all blood disorders.

We hope to provide assistance at all stages of treatment, recovery, after care, and the rehabilitation and resettlement of patients.

Registering as a donor is easy: any individual over age 18 can become a donor and be a part of the registry till the age of 60, provided they are healthy.

All that one needs is a simple mouth swab test and the consent to donate stem cells when the need arises. The swabs are sent to a highly-specialised laboratory in the US for HLA typing and the results shared with the worldwide registry maintained by WMDA.

Upon finding a match for a patient, the registry contacts the concerned donor.

The process is not complicated, it is exactly like platelet donation, only a few hours longer: avolunteer must undergo a complete medical check-up prior to donating stem cells and is put on stem cell boosting therapy for about four days before the procedure. No incision is involved and the donor does not require hospitalisation.

It just takes one day of your life and busy schedule to save a life.

***

Today, as I sat down to write this article, I also planned another kind of a celebration for Arjan's birthday on September 6: this year, we are holding a camp to bring about awareness about stem cells and register donors at a university in Noida.

Once again there is excitement, albeit of a different kind one held together with a sense of pathos.

Also read: Memories of my mother that Alzheimer's can't wipe clean

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My son died of cancer: Why I'm celebrating his birthday with stem cell awareness - DailyO

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Charles A. Goldthwaite, Jr., Ph.D.

In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined.

Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient's tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines. As an introduction to this exciting new field of stem cell research, this chapter will review the characteristics of iPSCs, the technical challenges that must be overcome before this strategy can be deployed, and the cells' potential applications to regenerative medicine.

As noted in other chapters, stem cells represent a precious commodity. Although present in embryonic and adult tissues, practical considerations such as obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells (see the Chapter, "Alternate Methods for Preparing Pluripotent Stem Cells" for details). As such, the logistical challenges of isolating, culturing, purifying, and differentiating stem cell lines that are extracted from tissues have led researchers to explore options for "creating" pluripotent cells using existing non-pluripotent cells. Coaxing abundant, readily available differentiated cells to pluripotency would in principle eliminate the search for rare cells while providing the opportunity to culture clinically useful quantities of stem-like cells.

One strategy to accomplish this goal is nuclear reprogramming, a technique that involves experimentally inducing a stable change in the nucleus of a mature cell that can then be maintained and replicated as the cell divides through mitosis. These changes are most frequently associated with the reacquisition of a pluripotent state, thereby endowing the cell with developmental potential. The strategy has historically been carried out using techniques such as somatic cell nuclear transfer (SCNT),1,2 altered nuclear transfer (ANT),3,4 and methods to fuse somatic cells with ESCs5,6 (see "Alternate Methods for Preparing Pluripotent Stem Cells" for details of these approaches). From a clinical perspective, these methods feature several drawbacks, such as the creation of an embryo or the development of hybrid cells that are not viable to treat disease. However, in 2006, these efforts informed the development of nuclear reprogramming in vitro, the breakthrough method that creates iPSCs.

This approach involves taking mature "somatic" cells from an adult and introducing the genes that encode critical transcription factor proteins, which themselves regulate the function of other genes important for early steps in embryonic development (See Fig. 10.1). In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem celllike state by forcing them to express genes important for maintaining the defining properties of ESCs.7 These factors were chosen because they were known to be involved in the maintenance of pluripotency, which is the capability to generate all other cell types of the body. The newly-created iPSCs were found to be highly similar to ESCs and could be established after several weeks in culture.7,8 In 2007, two different research groups reached a new milestone by deriving iPSCs from human cells, using either the original four genes9 or a different combination containing Oct4, Sox2, Nanog, and Lin28.10 Since then, researchers have reported generating iPSCs from somatic tissues of the monkey11 and rat.12,13

However, these original methods of reprogramming are inefficient, yielding iPSCs in less than 1% of the starting adult cells.14,15 The type of adult cell used also affects efficiency; fibroblasts require more time for factor expression and have lower efficiency of reprogramming than do human keratinocytes, mouse liver and stomach cells, or mouse neural stem cells.1419

Several approaches have been investigated to improve reprogramming efficiency and decrease potentially detrimental side effects of the reprogramming process. Since the retroviruses used to deliver the four transcription factors in the earliest studies can potentially cause mutagenesis (see below), researchers have investigated whether all four factors are absolutely necessary. In particular, the gene c-Myc is known to promote tumor growth in some cases, which would negatively affect iPSC usefulness in transplantation therapies. To this end, researchers tested a three-factor approach that uses the orphan nuclear receptor Esrrb with Oct4 and Sox2, and were able to convert mouse embryonic fibroblasts to iPSCs.20 This achievement corroborates other reports that c-Myc is dispensable for direct reprogramming of mouse fibroblasts.21 Subsequent studies have further reduced the number of genes required for reprogramming,2226 and researchers continue to identify chemicals that can either substitute for or enhance the efficiency of transcription factors in this process.27 These breakthroughs continue to inform and to simplify the reprogramming process, thereby advancing the field toward the generation of patient-specific stem cells for clinical application. However, as the next section will discuss, the method by which transcription factors are delivered to the somatic cells is critical to their potential use in the clinic.

Figure 10.1. Generating Induced Pluripotent Stem Cells (iPSCs).

2008 Terese Winslow

Reprogramming poses several challenges for researchers who hope to apply it to regenerative medicine. To deliver the desired transcription factors, the DNA that encodes their production must be introduced and integrated into the genome of the somatic cells. Early efforts to generate iPSCs accomplished this goal using retroviral vectors. A retrovirus is an RNA virus that uses an enzyme, reverse transcriptase, to replicate in a host cell and subsequently produce DNA from its RNA genome. This DNA incorporates into the host's genome, allowing the virus to replicate as part of the host cell's DNA. However, the forced expression of these genes cannot be controlled fully, leading to unpredictable effects.28 While other types of integrating viruses, such as lentiviruses, can increase the efficiency of reprogramming,16 the expression of viral transgenes remains a critical clinical issue. Given the dual needs of reducing the drawbacks of viral integration and maximizing reprogramming efficiency, researchers are exploring a number of strategies to reprogram cells in the absence of integrating viral vectors2730 or to use potentially more efficient integrative approaches.31,32

Before reprogramming can be considered for use as a clinical tool, the efficiency of the process must improve substantially. Although researchers have begun to identify the myriad molecular pathways that are implicated in reprogramming somatic cells,15 much more basic research will be required to identify the full spectrum of events that enable this process. Simply adding transcription factors to a population of differentiated cells does not guarantee reprogrammingthe low efficiency of reprogramming in vitro suggests that additional rare events are necessary to generate iPSCs, and the efficiency of reprogramming decreases even further with fibroblasts that have been cultured for long time periods.33 Furthermore, the differentiation stage of the starting cell appears to impact directly the reprogramming efficiency; mouse hematopoietic stem and progenitor cells give rise to iPSCs up to 300 times more efficiently than do their terminally-differentiated B- and T-cell counterparts.34 As this field continues to develop, researchers are exploring the reprogramming of stem or adult progenitor cells from mice24,25,34,35 and humans23,26 as one strategy to increase efficiency compared to that observed with mature cells.

As these discussions suggest, clinical application of iPSCs will require safe and highly efficient generation of stem cells. As scientists increase their understanding of the molecular mechanisms that underlie reprogramming, they will be able to identify the cell types and conditions that most effectively enable the process and use this information to design tools for widespread use. Clinical application of these cells will require methods to reprogram cells while minimizing DNA alterations. To this end, researchers have found ways to introduce combinations of factors in a single viral "cassette" into a known genetic location.36 Evolving tools such as these will enable researchers to induce programming more safely, thereby informing basic iPSC research and moving this technology closer to clinical application.

ESCs and iPSCs are created using different strategies and conditions, leading researchers to ask whether the cell types are truly equivalent. To assess this issue, investigators have begun extensive comparisons to determine pluripotency, gene expression, and function of differentiated cell derivatives. Ultimately, the two cell types exhibit some differences, yet they are remarkably similar in many key aspects that could impact their application to regenerative medicine. Future experiments will determine the clinical significance (if any) of the observed differences between the cell types.

Other than their derivation from adult tissues, iPSCs meet the defining criteria for ESCs. Mouse and human iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cell types from all three primitive embryonic layers, and displaying the capacity to contribute to many different tissues when injected into mouse embryos at a very early stage of development. Initially, it was unclear that iPSCs were truly pluripotent, as early iPSC lines contributed to mouse embryonic development but failed to produce live-born progeny as do ESCs. In late 2009, however, several research groups reported mouse iPSC lines that are capable of producing live births,37,38 noting that the cells maintain a pluripotent potential that is "very close to" that of ESCs.38 Therefore, iPSCs appear to be truly pluripotent, although they are less efficient than ESCs with respect to differentiating into all cell types.38 In addition, the two cell types appear to have similar defense mechanisms to thwart the production of DNA-damaging reactive oxygen species, thereby conferring the cells with comparable capabilities to maintain genomic integrity.39

Undifferentiated iPSCs appear molecularly indistinguishable from ESCs. However, comparative genomic analyses reveal differences between the two cell types. For example, hundreds of genes are differentially expressed in ESCs and iPSCs,40 and there appear to be subtle but detectable differences in epigenetic methylation between the two cell types.41,42 Genomic differences are to be expected; it has been reported that gene-expression profiles of iPSCs and ESCs from the same species differ no more than observed variability among individual ESC lines.43 It should be noted that the functional implications of these findings are presently unknown, and observed differences may ultimately prove functionally inconsequential.44

Recently, some of the researchers who first generated human iPSCs compared the ability of iPSCs and human ESCs to differentiate into neural cells (e.g., neurons and glia).45 Their results demonstrated that both cell types follow the same steps and time course during differentiation. However, although human ESCs differentiate into neural cells with a similar efficiency regardless of the cell line used, iPSC-derived neural cells demonstrate lower efficiency and greater variability when differentiating into neural cells. These observations occurred regardless of which of several iPSC-generation protocols were used to reprogram the original cell to the pluripotent state. Experimental evidence suggests that individual iPSC lines may be "epigenetically unique" and predisposed to generate cells of a particular lineage. However, the authors believe that improvements to the culturing techniques may be able to overcome the variability and inefficiency described in this report.

These findings underpin the importance of understanding the inherent variability among discrete cell populations, whether they are iPSCs or ESCs. Characterizing the variability among iPSC lines will be crucial to apply the cells clinically. Indeed, the factors that make each iPSC line unique may also delay the cells' widespread use, as differences among the cell lines will affect comparisons and potentially influence their clinical behavior. For example, successfully modeling disease requires being able to identify the cellular differences between patients and controls that lead to dysfunction. These differences must be framed in the context of the biologic variability inherent in a given patient population. If iPSC lines are to be used to model disease or screen candidate drugs, then variability among lines must be minimized and characterized fully so that researchers can understand how their observed results match to the biology of the disease being studied. As such, standardized assays and methods will become increasingly important for the clinical application of iPSCs, and controls must be developed that account for variability among the iPSCs and their derivatives.

Additionally, researchers must understand the factors that initiate reprogramming towards pluripotency in different cell types. A recent report has identified one factor that initiates reprogramming in human fibroblasts,46 setting the groundwork for developing predictive models to identify those cells that will become iPSCs. An iPSC may carry a genetic "memory" of the cell type that it once was, and this "memory" will likely influence its ability to be reprogrammed. Understanding how this memory varies among different cell types and tissues will be necessary to reprogram successfully.

iPSCs have the potential to become multipurpose research and clinical tools to understand and model diseases, develop and screen candidate drugs, and deliver cell-replacement therapy to support regenerative medicine. This section will explore the possibilities and the challenges that accompany these medical applications, with the caveat that some uses are more immediate than others. For example, researchers currently use stem cells to test/screen drugs or as study material to identify molecules or genes implicated in regeneration. Conducting experiments or testing candidate drugs on human cells grown in culture enables researchers to understand fundamental principles and relationships that will ultimately inform the use of stem cells as a source of tissue for transplantation. Therefore, using iPSCs in cell-replacement therapies is a future application of these cells, albeit one that has tremendous clinical potential. The following discussion will highlight recent efforts toward this goal while recognizing the challenges that must be overcome for these cells to reach the clinic.

Reprogramming technology offers the potential to treat many diseases, including Alzheimer's disease, Parkinson's disease, cardiovascular disease, diabetes, and amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease). In theory, easily-accessible cell types (such as skin fibroblasts) could be biopsied from a patient and reprogrammed, effectively recapitulating the patient's disease in a culture dish. Such cells could then serve as the basis for autologous cell replacement therapy. Because the source cells originate within the patient, immune rejection of the differentiated derivatives would be minimized. As a result, the need for immunosuppressive drugs to accompany the cell transplant would be lessened and perhaps eliminated altogether. In addition, the reprogrammed cells could be directed to produce the cell types that are compromised or destroyed by the disease in question. A recent experiment has demonstrated the proof of principle in this regard,47 as iPSCs derived from a patient with ALS were directed to differentiate into motor neurons, which are the cells that are destroyed in the disease.

Although much additional basic research will be required before iPSCs can be applied in the clinic, these cells represent multi-purpose tools for medical research. Using the techniques described in this article, researchers are now generating myriad disease-specific iPSCs. For example, dermal fibroblasts and bone marrow-derived mesencyhmal cells have been used to establish iPSCs from patients with a variety of diseases, including ALS, adenosine deaminase deficiency-related severe combined immunodeficiency, Shwachman- Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophies, Parkinson's disease, Huntington's disease, type 1 diabetes mellitus, Down syndrome/trisomy 21, and spinal muscular atrophy.4749 iPSCs created from patients diagnosed with a specific genetically-inherited disease can then be used to model disease pathology. For example, iPSCs created from skin fibroblasts taken from a child with spinal muscular atrophy were used to generate motor neurons that showed selective deficits compared to those derived from the child's unaffected mother.48 As iPSCs illuminate the development of normal and disease-specific pathologic tissues, it is expected that discoveries made using these cells will inform future drug development or other therapeutic interventions.

One particularly appealing aspect of iPSCs is that, in theory, they can be directed to differentiate into a specified lineage that will support treatment or tissue regeneration. Thus, somatic cells from a patient with cardiovascular disease could be used to generate iPSCs that could then be directed to give rise to functional adult cardiac muscle cells (cardiomyocytes) that replace diseased heart tissue, and so forth. Yet while iPSCs have great potential as sources of adult mature cells, much remains to be learned about the processes by which these cells differentiate. For example, iPSCs created from human50 and murine fibroblasts5153 can give rise to functional cardiomyocytes that display hallmark cardiac action potentials. However, the maturation process into cardiomyocytes is impaired when iPSCs are usedcardiac development of iPSCs is delayed compared to that seen with cardiomyocytes derived from ESCs or fetal tissue. Furthermore, variation exists in the expression of genetic markers in the iPSC-derived cardiac cells as compared to that seen in ESC-derived cardiomyocytes. Therefore, iPSC-derived cardiomyocytes demonstrate normal commitment but impaired maturation, and it is unclear whether observed defects are due to technical (e.g., incomplete reprogramming of iPSCs) or biological barriers (e.g., functional impairment due to genetic factors). Thus, before these cells can be used for therapy, it will be critical to distinguish between iPSC-specific and disease-specific phenotypes.

However, it must be noted that this emerging field is continually evolving; additional basic iPSC research will be required in parallel with the development of disease models. Although the reprogramming technology that creates iPSCs is currently imperfect, these cells will likely impact future therapy, and "imperfect" cells can illuminate many areas related to regenerative medicine. However, iPSC-derived cells that will be used for therapy will require extensive characterization relative to what is sufficient to support disease modeling studies. To this end, researchers have begun to use imaging techniques to observe cells that are undergoing reprogramming to distinguish true iPSCs from partially-reprogrammed cells.54 The potential for tumor formation must also be addressed fully before any iPSC derivatives can be considered for applied cell therapy. Furthermore, in proposed autologous therapy applications, somatic DNA mutations (e.g., non-inherited mutations that have accumulated during the person's lifetime) retained in the iPSCs and their derivatives could potentially impact downstream cellular function or promote tumor formation (an issue that may possibly be circumvented by creating iPSCs from a "youthful" cell source such as umbilical cord blood).55 Whether these issues will prove consequential when weighed against the cells' therapeutic potential remains to be determined. While the promise of iPSCs is great, the current levels of understanding of the cells' biology, variability, and utility must also increase greatly before iPSCs become standard tools for regenerative medicine.

Since their discovery four years ago, induced pluripotent stem cells have captured the imagination of researchers and clinicians seeking to develop patient-specific therapies. Reprogramming adult tissues to embryonic-like states has countless prospective applications to regenerative medicine, drug development, and basic research on stem cells and developmental processes. To this point, a PubMed search conducted in April 2010 using the term "induced pluripotent stem cells" (which was coined in 2006) returned more than 1400 publications, indicating a highly active and rapidlydeveloping research field.

However, many technical and basic science issues remain before the promise offered by iPSC technology can be realized fully. For putative regenerative medicine applications, patient safety is the foremost consideration. Standardized methods must be developed to characterize iPSCs and their derivatives. Furthermore, reprogramming has demonstrated a proof of-principle, yet the process is currently too inefficient for routine clinical application. Thus, unraveling the molecular mechanisms that govern reprogramming is a critical first step toward standardizing protocols. A grasp on the molecular underpinnings of the process will shed light on the differences between iPSCs and ESCs (and determine whether these differences are clinically significant). Moreover, as researchers delve more deeply into this field, the effects of donor cell populations can be compared to support a given application; i.e., do muscle-derived iPSCs produce more muscle than skin-derived cells? Based on the exciting developments in this area to date, induced pluripotent stem cells will likely support future therapeutic interventions, either directly or as research tools to establish novel models for degenerative disease that will inform drug development. While much remains to be learned in the field of iPSC research, the development of reprogramming techniques represents a breakthrough that will ultimately open many new avenues of research and therapy.

Chapter 9|Table of Contents|Chapter 11

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by David M. Panchision*

Diseases of the nervous system, including congenital disorders, cancers, and degenerative diseases, affect millions of people of all ages. Congenital disorders occur when the brain or spinal cord does not form correctly during development. Cancers of the nervous system result from the uncontrolled spread of aberrant cells. Degenerative diseases occur when the nervous system loses functioning of nerve cells. Most of the advances in stem cell research have been directed at treating degenerative diseases. While many treatments aim to limit the damage of these diseases, in some cases scientists believe that damage can be reversed by replacing lost cells with new ones derived from cells that can mature into nerve cells, called neural stem cells. Research that uses stem cells to treat nervous system disorders remains an area of great promise and challenge to demonstrate that cell-replacement therapy can restore lost function.

The nervous system is a complex organ made up of nerve cells (also called neurons) and glial cells, which surround and support neurons (see Figure 3.1). Neurons send signals that affect numerous functions including thought processes and movement. One type of glial cell, the oligodendrocyte, acts to speed up the signals of neurons that extend over long distances, such as in the spinal cord. The loss of any of these cell types may have catastrophic results on brain function.

Although reports dating back as early as the 1960s pointed towards the possibility that new nerve cells are formed in adult mammalian brains, this knowledge was not applied in the context of curing devastating brain diseases until the 1990s. While earlier medical research focused on limiting damage once it had occurred, in recent years researchers have been working hard to find out if the cells that can give rise to new neurons can be coaxed to restore brain function. New neurons in the adult brain arise from slowly-dividing cells that appear to be the remnants of stem cells that existed during fetal brain development. Since some of these adult cells still retain the ability to generate both neurons and glia, they are referred to as adult neural stem cells.

These findings are exciting because they suggest that the brain may contain a built-in mechanism to repair itself. Unfortunately, these new neurons are only generated in a few sites in the brain and turn into only a few specialized types of nerve cells. Although there are many different neuronal cell types in the brain, we now know that these new neurons can quot;plug inquot; correctly to assist brain function.1 The discovery of these cells has spurred further research into the characteristics of neural stem cells from the fetus and the adult, mostly using rodents and primates as model species. The hope is that these cells may be able to replenish those that are functionally lost in human degenerative diseases such as Parkinson's Disease, Huntington's Disease, and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), as well as from brain and spinal cord injuries that result from stroke or trauma.

Scientists are applying these new stem cell discoveries in two ways in their experiments. First, they are using current knowledge of normal brain development to modulate stem cells that are harvested and grown in culture. Researchers can then transplant these cultured cells into the brain of an animal model and allow the brain's own signals to differentiate the stem cells into neurons or glia. Alternatively, the stem cells can be induced to differentiate into neurons and glia while in the culture dish, before being transplanted into the brain. Much progress has been made the last several years with human embryonic stem (ES) cells that can differentiate into all cell types in the body. While ES cells can be maintained in culture for relatively long periods of time without differentiating, they usually must be coaxed through many more steps of differentiation to produce the desired cell types. Recent studies, however, suggest that ES cells may differentiate into neurons in a more straightforward manner than may other cell types.

Figure 3.1. The NeuronWhen sufficient neurotransmitters cross synapses and bind receptors on the neuronal cell body and dendrites, the neuron sends an electrical signal down its axon to synaptic terminals, which in turn release neurotransmitters into the synapse that affects the following neuron. The brain neurons that die in Parkinson's Disease release the transmitter dopamine. Oligodendrocytes supply the axon with an insulating myelin sheath.

2001 Terese Winslow

Second, scientists are identifying growth (trophic) factors that are normally produced and used by the developing and adult brain. They are using these factors to minimize damage to the brain and to activate the patient's own stem cells to repair damage that has occurred. Each of these strategies is being aggressively pursued to identify the most effective treatments for degenerative diseases. Most of these studies have been carried out initially with animal stem cells and recipients to determine their likelihood of success. Still, much more research is necessary to develop stem cell therapies that will be useful for treating brain and spinal cord disease in the same way that hematopoietic stem cell therapies are routinely used for immune system replacement (see Chapter 2).

The majority of stem cell studies of neurological disease have used rats and mice, since these models are convenient to use and are well-characterized biologically. If preliminary studies with rodent stem cells are successful, scientists will attempt to transplant human stem cells into rodents. Studies may then be carried out in primates (e.g., monkeys) to offer insight into how humans might respond to neurological treatment. Human studies are rarely undertaken until these other experiments have shown promising results. While human transplant studies have been carried out for decades in the case of Parkinson's disease, animal research continues to provide improved strategies to generate an abundant supply of transplantable cells.

The intensive research aiming at curing Parkinson's disease with stem cells is a good example for the various strategies, successful results, and remaining challenges of stem cell-based brain repair. Parkinson's disease is a progressive disorder of motor control that affects roughly 2% of persons 65 years and older. Triggered by the death of neurons in a brain region called the substantia nigra, Parkinson's disease begins with minor tremors that progress to limb and bodily rigidity and difficulty initiating movement. These neurons connect via long axons to another region called the striatum, composed of subregions called the caudate nucleus and the putamen. These neurons that reach from the substantia nigra to the striatum release the chemical transmitter dopamine onto their target neurons in the striatum. One of dopamine's major roles is to regulate the nerves that control body movement. As these cells die, less dopamine is produced, leading to the movement difficulties characteristic of Parkinson's disease. Currently, the causes of death of these neurons are not well understood.

For many years, doctors have treated Parkinson's disease patients with the drug levodopa (L-dopa), which the brain converts into dopamine. Although the drug works well initially, levodopa eventually loses its effectiveness, and side-effects increase. Ultimately, many doctors and patients find themselves fighting a losing battle. For this reason, a huge effort is underway to develop new treatments, including growth factors that help the remaining dopamine neurons survive and transplantation procedures to replace those that have died.

The strategy to use new cells to replace lost ones is not new. Surgeons first attempted to transplant dopamine-releasing cells from a patient's own adrenal glands in the 1980s.2,3 Although one of these studies reported a dramatic improvement in the patients' conditions, U.S. surgeons were only able to achieve modest and temporary improvement, insufficient to outweigh the risks of such a procedure. As a result, these human studies were not pursued further.

Another strategy was attempted in the 1970s, in which cells derived from fetal tissue from the mouse substantia nigra was transplanted into the adult rat eye and found to develop into mature dopamine neurons.4 In the 1980s, several groups showed that transplantation of this type of tissue could reverse Parkinson's-like symptoms in rats and monkeys when placed in the damaged areas.The success of the animal studies led to several human trials beginning in the mid-1980s.5,6 In some cases, patients showed a lessening of their symptoms. Also, researchers could measure an increase in dopamine neuron function in the striatum of these patients by using a brain-imaging method called positron emission tomography (PET) (see Figure 3.2).7

The NIH has funded two large and well-controlled clinical trials in the past 15 years in which researchers transplanted tissue from aborted fetuses into the striatum of patients with Parkinson's disease.7,8 These studies, performed in Colorado and New York, included controls where patients received quot;shamquot; surgery (no tissue was implanted), and neither the patients nor the scientists who evaluated their progress knew which patients received the implants. The patients' progress was followed for up to eight years. Unfortunately, both studies showed that the transplants offered little benefit to the patients as a group. While some patients showed improvement, others began to suffer from dyskinesias, jerky involuntary movements that are often side effects of long-term L-dopa treatment. This effect occurred in 15% of the patients in the Colorado study.7 and more than half of the patients in the New York study.8 Additionally, the New York study showed evidence that some patients' immune systems were attacking the grafts.

However, promising findings emerged from these studies as well. Younger and milder Parkinson's patients responded relatively well to the grafts, and PET scans of patients showed that some of the transplanted dopamine neurons survived and matured. Additionally, autopsies on three patients who died of unrelated causes, years after the surgeries, indicated the presence of dopamine neurons from the graft. These cells appeared to have matured in the same way as normal dopamine neurons, which suggested that they were acting normally in the brain.

Figure 3.2. Positron Emission Tomography (PET) images from a Parkinson's patient before and after fetal tissue transplantation. The image taken before surgery (left) shows uptake of a radioactive form of dopamine (red) only in the caudate nucleus, indicating that dopamine neurons have degenerated. Twelve months after surgery, an image from the same patient (right) reveals increased dopamine function, especially in the putamen. (Reprinted with permission from N Eng J Med 2001;344(10) p. 710.)

Researchers in Sweden followed the severity of dyskinesia in patients for eleven years after neural transplantation and found that the severity was typically mild or moderate. These results suggested that dyskinesias were due to effects that were distinct from the beneficial effects of the grafts.9 Dyskinesias may therefore be related to the ways that transplantation disturbs other cells in the brain and so may be minimized by future improvements in therapy. Another study that involved the grafting of cells both into the striatum (the target of dopamine neurons) and the substantia nigra (where dopamine neurons normally reside) of three patients showed no adverse effects and some modest improvement in patient movement.10 To determine the full extent of therapeutic benefits from such a procedure and confirm the reliability of these results, this study will need to be repeated with a larger patient population that includes the appropriate controls.

The limited success of these studies may reflect variations in the fetal tissue used for transplantation, which is of limited quantity and can not be standardized or well-characterized. The full complement of cells in these fetal tissue samples is not known at present. As a result, the tissue remains the greatest source of uncertainty in patient outcome following transplantation.

The major goal for Parkinson's investigators is to generate a source of cells that can be grown in large supply, maintained indefinitely in the laboratory, and differentiated efficiently into dopamine neurons that work when transplanted into the brain of a Parkinson's patient. Scientists have investigated the behavior of stem cells in culture and the mechanisms that govern dopamine neuron production during development in their attempts to identify optimal culture conditions that allow stem cells to turn into dopamine-producing neurons.

Preliminary studies have been carried out using immature stem cell-like precursors from the rodent ventral midbrain, the region that normally gives rise to these dopamine neurons. In one study these precursors were turned into functional dopamine neurons, which were then grafted into rats previously treated with 6-hydroxy-dopamine (6-OHDA) to kill the dopamine neurons in their substantia nigra and induce Parkinson's-like symptoms. Even though the percentage of surviving dopamine neurons was low following transplantation, it was sufficient to relieve the Parkinson's-like symptoms.11 Unfortunately, these fetal cells cannot be maintained in culture for very long before they lose the ability to differentiate into dopamine neurons.

Cells with features of neural stem cells have been derived from ES-cells, fetal brain tissue, brain tissue from neurosurgery, and brain tissue that was obtained after a person's death. There is controversy about whether other organ stem cell populations, such as hematopoietic stem cells, either contain or give rise to neural stem cells

Many researchers believe that the more primitive ES cells may be an excellent source of dopamine neurons because ES-cells can be grown indefinitely in a laboratory dish and can differentiate into any cell type, even after long periods in culture. Mouse ES cells injected directly into 6-OHDA-treated rat brains led to relief of Parkinson-like symptoms. Further investigation showed that these ES cells had differentiated into both dopamine and serotonin neurons.12 This latter type of neuron is generated in an adjacent region of the brain and may complicate the response to transplantation. Since ES cells can generate all cell types in the body, unwanted cell types such as muscle or bone could theoretically also be introduced into the brain. As a result, a great deal of effort is being currently put into finding the right quot;recipequot; for turning ES cells into dopamine neuronsand only this cell typeto treat Parkinson's disease. Researchers strive to learn more about normal brain development to help emulate the natural progression of ES cells toward dopamine neurons in the culture dish.

The recent availability of human ES cells has led to further studies to examine their potential for differentiation into dopamine neurons. Recently, dopamine neurons from human embryonic stem cells have been generated.13 One research group used a special type of companion cell, along with specific growth factors, to promote the differentiation of the ES cells through several stages into dopamine neurons. These neurons showed many of the characteristic properties of normal dopamine neurons.13 Furthermore, recent evidence of more direct neuronal differentiation methods from mouse ES cells fuels hope that scientists can refine and streamline the production of transplantable human dopamine neurons.

One method with great therapeutic potential is nuclear transfer. This method fuses the genetic material from one individual donor with a recipient egg cell that has had its nucleus removed. The early embryo that develops from this fusion is a genetic match for the donor. This process is sometimes called quot;therapeutic cloningquot; and is regarded by some to be ethically questionable. However, mouse ES cells have been differentiated successfully in this way into dopamine neurons that corrected Parkinsonian symptoms when transplanted into 6-OHDA-treated rats.14 Similar results have been obtained using parthenogenetic primate stem cells, which are cells that are genetic matches from a female donor with no contribution from a male donor.15 These approaches may offer the possibility of treating patients with genetically-matched cells, thereby eliminating the possibility of graft rejection.

Scientists are also studying the possibility that the brain may be able to repair itself with therapeutic support. This avenue of study is in its early stages but may involve administering drugs that stimulate the birth of new neurons from the brain's own stem cells. The concept is based on research showing that new nerve cells are born in the adult brains of humans. The phenomenon occurs in a brain region called the dentate gyrus of the hippocampus. While it is not yet clear how these new neurons contribute to normal brain function, their presence suggests that stem cells in the adult brain may have the potential to re-wire dysfunctional neuronal circuitry.

The adult brain's capacity for self-repair has been studied by investigating how the adult rat brain responds to transforming growth factor alpha (TGF), a protein important for early brain development that is expressed in limited quantities in adults.16 Injection of TGF into a healthy rat brain causes stem cells to divide for several days before ceasing division. In 6-OHDAtreated (Parkinsonian) rats, however, the cells proliferated and migrated to the damaged areas. Surprisingly, the TGF-treated rats showed few of the behavioral problems associated with untreated Parkinsonian rats.16 Additionally, in 2002 and 2003, two research groups isolated small numbers of dividing cells in the substantia nigra of adult rodents.17,18

These findings suggest that the brain can repair itself, as long as the repair process is triggered sufficiently. It is not clear, though, whether stem cells are responsible for this repair or if the TGF activates a different repair mechanism.

Many other diseases that affect the nervous system hold the potential for being treated with stem cells. Experimental therapies for chronic diseases of the nervous system, such as Alzheimer's disease, Lou Gehrig's disease, or Huntington's disease, and for acute injuries, such as spinal cord and brain trauma or stoke, are being currently developed and tested. These diverse disorders must be investigated within the contexts of their unique disease processes and treated accordingly with highly adapted cell-based approaches.

Although severe spinal cord injury is an area of intense research, the therapeutic targets are not as clear-cut as in Parkinson's disease. Spinal cord trauma destroys numerous cell types, including the neurons that carry messages between the brain and the rest of the body. In many spinal injuries, the cord is not actually severed, and at least some of the signal-carrying neuronal axons remain intact. However, the surviving axons no longer carry messages because oligodendrocytes, which make the axons' insulating myelin sheath, are lost. Researchers have recently made progress to replenish these lost myelin-producing cells. In one study, scientists cultured human ES cells through several steps to make mixed cultures that contained oligodendrocytes. When they injected these cells into the spinal cords of chemically-demyelinated rats, the treated rats regained limited use of their hind limbs compared with un-grafted rats.19 Researchers are not certain, however, whether the limited increase in function observed in rats is actually due to the remyelination or to an unidentified trophic effect of the treatment.

Getting neurons to grow new axons through the injury site to reconnect with their targets is even more challenging. While myelin promotes normal neuronal function, it also inhibits the growth of new axons following spinal injury. In a recent study to attempt post-trauma axonal growth, Harper and colleagues treated ES cells with a combination of factors that are known to promote motor neuron differentiation.20 The researchers then transplanted these cells into adult rats that had received spinal cord injuries. While many of these cells survived and differentiated into neurons, they did not send out axons unless the researchers also added drugs that interfered with the inhibitory effects of myelin. The growth effect was modest, and the researchers have not yet seen evidence of functional neuron connections. However, their results raise the possibility that signals can be turned on and off in the correct order to allow neurons to reconnect and function properly. Spinal injury researchers emphasize that additional basic and preclinical research must be completed before attempting human trials using stem cell therapies to repair the trauma-damaged nervous system.

Since myelin loss is at the heart of many other degenerative diseases, oligodendrocytes made from ES cells may be useful to treat these conditions as well. For example, scientists recently cultured human ES cells with a combination of growth factors to generate a highly enriched population of myelinating oligodendrocyte precursors.21,22 The researchers then tested these cells in a genetically-mutated mouse that does not produce myelin properly. When the growth factor-cultured ES cells were transplanted into affected mice, the cells migrated and differentiated into mature oligodendrocytes that made myelin sheaths around neighboring axons. These researchers subsequently showed that these cells matured and improved movement when grafted in rats with spinal cord injury.23 Improved movement only occurred when grafting was completed soon after injury, suggesting that some post-injury responses may interfere with the grafted cells. However, these results are sufficiently encouraging to plan clinical trials to test whether replacement of myelinating glia can treat spinal cord injury.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is characterized by a progressive destruction of motor neurons in the spinal cord. Patients with ALS develop increasing muscle weakness over time, which ultimately leads to paralysis and death. The cause of ALS is largely unknown, and there are no effective treatments. Researchers recently have used different sources of stem cells to test in rat models of ALS to test for possible nerve cell-restoring properties. In one study, researchers injected cell clusters made from embryonic germ (EG) cells into the spinal cord fluid of the partially-paralyzed rats.24 Three months after the injections, many of the treated rats were able to move their hind limbs and walk with difficulty, while the rats that did not receive cell injections remained paralyzed. Moreover, the transplanted cells had migrated throughout the spinal fluid and developed into cells that displayed molecular characteristics of mature motor neurons. However, too few cells matured in this way to account for the recovery, and there was no evidence that the transplanted cells formed functional connections with muscles. The researchers suggest that the transplanted cells may be promoting recovery in some other way, such as by producing trophic factors.

This possibility was addressed in a second study in which scientists grew human fetal CNS stem cells in culture and genetically modified them to produce a trophic factor that promotes the survival of cells that are lost in ALS. When grafted into the spinal cords of the ALS-like rats, these cells secreted the desired growth factor and promoted the survival of the neurons that are normally lost in the ALS-like rats.25 While promising, these results highlight the need for additional basic research into functional recovery in ALS disease models.

Stroke affects about 750,000 patients per year in the

U.S. and is the most common cause of disability in adults. A stroke occurs when blood flow to the brain is disrupted. As a consequence, cells in affected brain regions die from insufficient amounts of oxygen. The treatment of stroke with anti-clotting drugs has dramatically improved the odds of patient recovery. However, in many patients the damage cannot be prevented, and the patient may permanently lose the functions of affected areas of the brain. For these patients, researchers are now considering stem cells as a way to repair the damaged brain regions. This problem is made more challenging because the damage in stroke may be widespread and may affect many cell types and connections.

However, researchers from Sweden recently observed that strokes in rats cause the brain's own stem cells to divide and give rise to new neurons.26 However, these neurons, which survived only a couple of weeks, are few in number compared to the extent of damage caused. A group from the University of Tokyo added a growth factor, bFGF, into the brains of rats after stroke and showed that the hippocampus was able to generate large numbers of new neurons.27 The researchers found evidence that these new neurons were actually making connections with other neurons. These and other results suggest that future stroke treatments may be able to coax the brain's own stem cells to make replacement neurons.

Taking an alternative approach, another group attempted transplantation as a means to treat the loss of brain mass after a severe stroke. By adding stem cells onto a polymer scaffold that they implanted into the stroke-damaged brains of mice, the researchers demonstrated that the seeded stem cells differentiated into neurons and that the polymer scaffold reduced scarring.28 Two groups transplanted human fetal stem cells in independent studies into the brains of stroke-affected rodents; these stem cells not only survived but migrated to the damaged areas of the brain.29,30 These studies increase our knowledge of how stem cells are attracted to diseased areas of the brain.

There is also increasing evidence from numerous animal disease models that stem cells are actively drawn to brain damage. Once they reach these damaged areas, they have been shown to exert beneficial effects such as reducing brain inflammation or supporting nerve cells. It is hoped that, once these mechanisms are better understood, this stem cell recruitment can potentially be exploited to mobilize a patient's own stem cells.

Similar lines of research are being considered with other disorders such as Huntington's Disease and certain congenital defects. While much attention has been called to the treatment of Alzheimer's Disease, it is still not clear if stem cells hold the key to its treatment. But despite the fact that much basic work remains and many fundamental questions are yet to be answered, researchers are hopeful that repair for once-incurable nervous system disorders may be amenable to stem cell based therapies.

Considerable progress has been made the last few years in our understanding of stem cell biology and devising sources of cells for transplantation. New methods are also being developed for cell delivery and targeting to affected areas of the body. These advances have fueled optimism that new treatments will come for millions of persons who suffer from neurological disorders. But it is the current task of scientists to bring these methods from the laboratory bench to the clinic in a scientifically sound and ethically acceptable fashion.

Notes:

* Chief, Developmental Neurobiology Program, Molecular, Cellular & Genomic Neuroscience Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health, Email: panchisiond@mail.nih.gov

Chapter 2|Table of Contents|Chapter 4

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Repairing the Nervous System with Stem Cells | stemcells ...

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NEW YORK--(BUSINESS WIRE)--Americord, the fastest growing cord blood bank in the country, and a leader in the advancement of umbilical cord blood, cord tissue, and placental tissue banking, has expanded customer options to now offer placental tissue banking as a stand-alone service.

As one of the only companies to offer placental tissue banking, Americord believes in the importance of offering new mothers an opportunity to preserve their stem cells for potential future use. We are therefore launching placental tissue banking as a stand-alone service, without the need to bank umbilical cord blood.

While many families have embraced Americords cord blood and tissue bundles, some have expressed interest in storing only placental tissue, commented Erin Willigan, Vice-President of Marketing at Americord. We wanted to respond to their desire to select individual services that best fit their budget and future plans.

Placental tissue contains mesenchymal stem cells (MSCs) that are a genetic match to the mother. These stem cells are multipotent, meaning that they can differentiate into many different types of cells, including organ and muscle tissue, skin, bone, cartilage, and fat cells. The placenta uses these stem cells to grow and function during pregnancy. After baby is delivered, stem cells from the placenta can be collected and stored for potential future use.

Due to their ability to multiply and become many different types of tissue, MSCs hold great promise for regenerative treatments. Over 50 clinical trials are currently researching therapeutic uses for MSCs, including treatments for Type 1 Diabetes, Alzheimers, and spinal cord injuries.

About Americord Registry LLC (Americord)

Americord Registry LLC is a leader in the advancement of umbilical cord blood, cord tissue and placenta tissue banking. Americord collects, processes, and stores newborn stem cells from umbilical cord blood for future medical or therapeutic use, including the treatment of more than 80 blood diseases such as sickle cell anemia and leukemia. Founded in 2008, Americord is registered with the FDA and operates in all 50 states. The companys laboratory is CLIA Certified, accredited by the AABB and complies with all federal and state guidelines and applicable licenses. Americord is headquartered in New York, NY. For more information, visit http://www.americordblood.com.

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This article is about imaging techniques and modalities for the human body. For imaging of animals in research, see Preclinical imaging.

Medical imaging is the technique and process of creating visual representations of the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to reveal internal structures hidden by the skin and bones, as well as to diagnose and treat disease. Medical imaging also establishes a database of normal anatomy and physiology to make it possible to identify abnormalities. Although imaging of removed organs and tissues can be performed for medical reasons, such procedures are usually considered part of pathology instead of medical imaging.

As a discipline and in its widest sense, it is part of biological imaging and incorporates radiology which uses the imaging technologies of X-ray radiography, magnetic resonance imaging, medical ultrasonography or ultrasound, endoscopy, elastography, tactile imaging, thermography, medical photography and nuclear medicine functional imaging techniques as positron emission tomography (PET) and Single-photon emission computed tomography (SPECT).

Measurement and recording techniques which are not primarily designed to produce images, such as electroencephalography (EEG), magnetoencephalography (MEG), electrocardiography (ECG), and others represent other technologies which produce data susceptible to representation as a parameter graph vs. time or maps which contain data about the measurement locations. In a limited comparison these technologies can be considered as forms of medical imaging in another discipline.

Up until 2010, 5billion medical imaging studies had been conducted worldwide.[1] Radiation exposure from medical imaging in 2006 made up about 50% of total ionizing radiation exposure in the United States.[2]

Medical imaging is often perceived to designate the set of techniques that noninvasively produce images of the internal aspect of the body. In this restricted sense, medical imaging can be seen as the solution of mathematical inverse problems. This means that cause (the properties of living tissue) is inferred from effect (the observed signal). In the case of medical ultrasonography, the probe consists of ultrasonic pressure waves and echoes that go inside the tissue to show the internal structure. In the case of projectional radiography, the probe uses X-ray radiation, which is absorbed at different rates by different tissue types such as bone, muscle and fat.

The term noninvasive is used to denote a procedure where no instrument is introduced into a patients body which is the case for most imaging techniques used.

In the clinical context, invisible light medical imaging is generally equated to radiology or clinical imaging and the medical practitioner responsible for interpreting (and sometimes acquiring) the images is a radiologist. Visible light medical imaging involves digital video or still pictures that can be seen without special equipment. Dermatology and wound care are two modalities that use visible light imagery. Diagnostic radiography designates the technical aspects of medical imaging and in particular the acquisition of medical images. The radiographer or radiologic technologist is usually responsible for acquiring medical images of diagnostic quality, although some radiological interventions are performed by radiologists.

As a field of scientific investigation, medical imaging constitutes a sub-discipline of biomedical engineering, medical physics or medicine depending on the context: Research and development in the area of instrumentation, image acquisition (e.g., radiography), modeling and quantification are usually the preserve of biomedical engineering, medical physics, and computer science; Research into the application and interpretation of medical images is usually the preserve of radiology and the medical sub-discipline relevant to medical condition or area of medical science (neuroscience, cardiology, psychiatry, psychology, etc.) under investigation. Many of the techniques developed for medical imaging also have scientific and industrial applications.[3]

Two forms of radiographic images are in use in medical imaging. Projection radiography and fluoroscopy, with the latter being useful for catheter guidance. These 2D techniques are still in wide use despite the advance of 3D tomography due to the low cost, high resolution, and depending on application, lower radiation dosages. This imaging modality utilizes a wide beam of x rays for image acquisition and is the first imaging technique available in modern medicine.

A magnetic resonance imaging instrument (MRI scanner), or nuclear magnetic resonance (NMR) imaging scanner as it was originally known, uses powerful magnets to polarize and excite hydrogen nuclei (i.e., single protons) of water molecules in human tissue, producing a detectable signal which is spatially encoded, resulting in images of the body.[4] The MRI machine emits a radio frequency (RF) pulse at the resonant frequency of the hydrogen atoms on water molecules. Radio frequency antennas (RF coils) send the pulse to the area of the body to be examined. The RF pulse is absorbed by protons, causing their direction with respect to the primary magnetic field to change. When the RF pulse is turned off, the protons relax back to alignment with the primary magnet and emit radio-waves in the process. This radio-frequency emission from the hydrogen-atoms on water is what is detected and reconstructed into an image. The resonant frequency of a spinning magnetic dipole (of which protons are one example) is called the Larmor frequency and is determined by the strength of the main magnetic field and the chemical environment of the nuclei of interest. MRI uses three electromagnetic fields: a very strong (typically 1.5 to 3 teslas) static magnetic field to polarize the hydrogen nuclei, called the primary field; gradient fields that can be modified to vary in space and time (on the order of 1kHz) for spatial encoding, often simply called gradients; and a spatially homogeneous radio-frequency (RF) field for manipulation of the hydrogen nuclei to produce measurable signals, collected through an RF antenna.

Like CT, MRI traditionally creates a two dimensional image of a thin slice of the body and is therefore considered a tomographic imaging technique. Modern MRI instruments are capable of producing images in the form of 3D blocks, which may be considered a generalization of the single-slice, tomographic, concept. Unlike CT, MRI does not involve the use of ionizing radiation and is therefore not associated with the same health hazards. For example, because MRI has only been in use since the early 1980s, there are no known long-term effects of exposure to strong static fields (this is the subject of some debate; see Safety in MRI) and therefore there is no limit to the number of scans to which an individual can be subjected, in contrast with X-ray and CT. However, there are well-identified health risks associated with tissue heating from exposure to the RF field and the presence of implanted devices in the body, such as pace makers. These risks are strictly controlled as part of the design of the instrument and the scanning protocols used.

Because CT and MRI are sensitive to different tissue properties, the appearance of the images obtained with the two techniques differ markedly. In CT, X-rays must be blocked by some form of dense tissue to create an image, so the image quality when looking at soft tissues will be poor. In MRI, while any nucleus with a net nuclear spin can be used, the proton of the hydrogen atom remains the most widely used, especially in the clinical setting, because it is so ubiquitous and returns a large signal. This nucleus, present in water molecules, allows the excellent soft-tissue contrast achievable with MRI.

A number of different pulse sequences can be used for specific MRI diagnostic imaging (multiparametric MRI or mpMRI). It is possible to differentiate tissue characteristics by combining two or more of the following imaging sequences, depending on the information being sought: T1-weighted (T1-MRI), T2-weighted (T2-MRI), diffusion weighted imaging (DWI-MRI), dynamic contrast enhancement (DCE-MRI), and spectroscopy (MRI-S). For example, imaging of prostate tumors is better accomplished using T2-MRI and DWI-MRI than T2-weighted imaging alone.[5] The number of applications of mpMRI for detecting disease in various organs continues to expand, including liver studies, breast tumors, pancreatic tumors, and assessing the effects of vascular disruption agents on cancer tumors.[6][7][8]

Nuclear medicine encompasses both diagnostic imaging and treatment of disease, and may also be referred to as molecular medicine or molecular imaging & therapeutics.[9] Nuclear medicine uses certain properties of isotopes and the energetic particles emitted from radioactive material to diagnose or treat various pathology. Different from the typical concept of anatomic radiology, nuclear medicine enables assessment of physiology. This function-based approach to medical evaluation has useful applications in most subspecialties, notably oncology, neurology, and cardiology. Gamma cameras and PET scanners are used in e.g. scintigraphy, SPECT and PET to detect regions of biologic activity that may be associated with disease. Relatively short lived isotope, such as 99mTc is administered to the patient. Isotopes are often preferentially absorbed by biologically active tissue in the body, and can be used to identify tumors or fracture points in bone. Images are acquired after collimated photons are detected by a crystal that gives off a light signal, which is in turn amplified and converted into count data.

Fiduciary markers are used in a wide range of medical imaging applications. Images of the same subject produced with two different imaging systems may be correlated (called image registration) by placing a fiduciary marker in the area imaged by both systems. In this case, a marker which is visible in the images produced by both imaging modalities must be used. By this method, functional information from SPECT or positron emission tomography can be related to anatomical information provided by magnetic resonance imaging (MRI).[12] Similarly, fiducial points established during MRI can be correlated with brain images generated by magnetoencephalography to localize the source of brain activity.

Medical ultrasonography uses high frequency broadband sound waves in the megahertz range that are reflected by tissue to varying degrees to produce (up to 3D) images. This is commonly associated with imaging the fetus in pregnant women. Uses of ultrasound are much broader, however. Other important uses include imaging the abdominal organs, heart, breast, muscles, tendons, arteries and veins. While it may provide less anatomical detail than techniques such as CT or MRI, it has several advantages which make it ideal in numerous situations, in particular that it studies the function of moving structures in real-time, emits no ionizing radiation, and contains speckle that can be used in elastography. Ultrasound is also used as a popular research tool for capturing raw data, that can be made available through an ultrasound research interface, for the purpose of tissue characterization and implementation of new image processing techniques. The concepts of ultrasound differ from other medical imaging modalities in the fact that it is operated by the transmission and receipt of sound waves. The high frequency sound waves are sent into the tissue and depending on the composition of the different tissues; the signal will be attenuated and returned at separate intervals. A path of reflected sound waves in a multilayered structure can be defined by an input acoustic impedance (ultrasound sound wave) and the Reflection and transmission coefficients of the relative structures.[11] It is very safe to use and does not appear to cause any adverse effects. It is also relatively inexpensive and quick to perform. Ultrasound scanners can be taken to critically ill patients in intensive care units, avoiding the danger caused while moving the patient to the radiology department. The real time moving image obtained can be used to guide drainage and biopsy procedures. Doppler capabilities on modern scanners allow the blood flow in arteries and veins to be assessed.

Elastography is a relatively new imaging modality that maps the elastic properties of soft tissue. This modality emerged in the last two decades. Elastography is useful in medical diagnoses, as elasticity can discern healthy from unhealthy tissue for specific organs/growths. For example, cancerous tumours will often be harder than the surrounding tissue, and diseased livers are stiffer than healthy ones.[13][14][15][16] There are a several elastographic techniques based on the use of ultrasound, magnetic resonance imaging and tactile imaging. The wide clinical use of ultrasound elastography is a result of the implementation of technology in clinical ultrasound machines. Main branches of ultrasound elastography include Quasistatic Elastography/Strain Imaging, Shear Wave Elasticity Imaging (SWEI), Acoustic Radiation Force Impulse imaging (ARFI), Supersonic Shear Imaging (SSI), and Transient Elastography.[14] In the last decade a steady increase of activities in the field of elastography is observed demonstrating successful application of the technology in various areas of medical diagnostics and treatment monitoring.

Tactile imaging is a medical imaging modality that translates the sense of touch into a digital image. The tactile image is a function of P(x,y,z), where P is the pressure on soft tissue surface under applied deformation and x,y,z are coordinates where pressure P was measured. Tactile imaging closely mimics manual palpation, since the probe of the device with a pressure sensor array mounted on its face acts similar to human fingers during clinical examination, slightly deforming soft tissue by the probe and detecting resulting changes in the pressure pattern. Figure on the right presents an experiment on a composite tissue phantom examined by a tactile imaging probe illustrating the ability of tactile imaging to visualize in 3D the structure of the object.

This modality is used for imaging of the prostate,[17] breast,[18]vagina and pelvic floor support structures,[19] and myofascial trigger points in muscle.[20]

Photoacoustic imaging is a recently developed hybrid biomedical imaging modality based on the photoacoustic effect. It combines the advantages of optical absorption contrast with ultrasonic spatial resolution for deep imaging in (optical) diffusive or quasi-diffusive regime. Recent studies have shown that photoacoustic imaging can be used in vivo for tumor angiogenesis monitoring, blood oxygenation mapping, functional brain imaging, and skin melanoma detection, etc.

Tomography is the imaging by sections or sectioning. The main such methods in medical imaging are:

When ultrasound is used to image the heart it is referred to as an echocardiogram. Echocardiography allows detailed structures of the heart, including chamber size, heart function, the valves of the heart, as well as the pericardium (the sac around the heart) to be seen. Echocardiography uses 2D, 3D, and Doppler imaging to create pictures of the heart and visualize the blood flowing through each of the four heart valves. Echocardiography is widely used in an array of patients ranging from those experiencing symptoms, such as shortness of breath or chest pain, to those undergoing cancer treatments. Transthoracic ultrasound has been proven to be safe for patients of all ages, from infants to the elderly, without risk of harmful side effects or radiation, differentiating it from other imaging modalities. Echocardiography is one of the most commonly used imaging modalities in the world due to its portability and use in a variety of applications. In emergency situations, echocardiography is quick, easily accessible, and able to be performed at the bedside, making it the modality of choice for many physicians.

FNIR Is a relatively new non-invasive imaging technique. NIRS (near infrared spectroscopy) is used for the purpose of functional neuroimaging and has been widely accepted as a brain imaging technique.[21]

Using superparamagnetic iron oxide nanoparticles, magnetic particle imaging (MPI) is a developing diagnostic imaging technique used for tracking superparamagnetic iron oxide nanoparticles. The primary advantage is the high sensitivity and specificity, along with the lack of signal decrease with tissue depth. MPI has been used in medical research to image cardiovascular performance, neuroperfusion, and cell tracking.

In response to increased concern by the public over radiation doses and the ongoing progress of best practices, The Alliance for Radiation Safety in Pediatric Imaging was formed within the Society for Pediatric Radiology. In concert with The American Society of Radiologic Technologists, The American College of Radiology and The American Association of Physicists in Medicine, the Society for Pediatric Radiology developed and launched the Image Gently Campaign which is designed to maintain high quality imaging studies while using the lowest doses and best radiation safety practices available on pediatric patients.[22] This initiative has been endorsed and applied by a growing list of various Professional Medical organizations around the world and has received support and assistance from companies that manufacture equipment used in Radiology.

Following upon the success of the Image Gently campaign, the American College of Radiology, the Radiological Society of North America, the American Association of Physicists in Medicine and the American Society of Radiologic Technologists have launched a similar campaign to address this issue in the adult population called Image Wisely.[23] The World Health Organization and International Atomic Energy Agency (IAEA) of the United Nations have also been working in this area and have ongoing projects designed to broaden best practices and lower patient radiation dose.[24][25][26]

Medical imaging may be indicated in pregnancy because of pregnancy complications, intercurrent diseases or routine prenatal care. Magnetic resonance imaging (MRI) without MRI contrast agents as well as obstetric ultrasonography are not associated with any risk for the mother or the fetus, and are the imaging techniques of choice for pregnant women.[27]Projectional radiography, X-ray computed tomography and nuclear medicine imaging result some degree of ionizing radiation exposure, but have with a few exceptions much lower absorbed doses than what are associated with fetal harm.[27] At higher dosages, effects can include miscarriage, birth defects and intellectual disability.[27]

The amount of data obtained in a single MR or CT scan is very extensive. Some of the data that radiologists discard could save patients time and money, while reducing their exposure to radiation and risk of complications from invasive procedures.[28] Another approach for making the procedures more efficient is based on utilizing additional constraints, e.g., in some medical imaging modalities one can improve the efficiency of the data acquisition by taking into account the fact the reconstructed density is positive.[29]

Volume rendering techniques have been developed to enable CT, MRI and ultrasound scanning software to produce 3D images for the physician.[30] Traditionally CT and MRI scans produced 2D static output on film. To produce 3D images, many scans are made, then combined by computers to produce a 3D model, which can then be manipulated by the physician. 3D ultrasounds are produced using a somewhat similar technique. In diagnosing disease of the viscera of abdomen, ultrasound is particularly sensitive on imaging of biliary tract, urinary tract and female reproductive organs (ovary, fallopian tubes). As for example, diagnosis of gall stone by dilatation of common bile duct and stone in common bile duct. With the ability to visualize important structures in great detail, 3D visualization methods are a valuable resource for the diagnosis and surgical treatment of many pathologies. It was a key resource for the famous, but ultimately unsuccessful attempt by Singaporean surgeons to separate Iranian twins Ladan and Laleh Bijani in 2003. The 3D equipment was used previously for similar operations with great success.

Other proposed or developed techniques include:

Some of these techniques[examples needed] are still at a research stage and not yet used in clinical routines.

Neuroimaging has also been used in experimental circumstances to allow people (especially disabled persons) to control outside devices, acting as a brain computer interface.

Many medical imaging software applications (3DSlicer, ImageJ, MIPAV, ImageVis3D, etc.) are used for non-diagnostic imaging, specifically because they dont have an FDA approval[31] and not allowed to use in clinical research for patient diagnosis.[32] Note that many clinical research studies are not designed for patient diagnosis anyway.[33]

Used primarily in ultrasound imaging, capturing the image produced by a medical imaging device is required for archiving and telemedicine applications. In most scenarios, a frame grabber is used in order to capture the video signal from the medical device and relay it to a computer for further processing and operations.[34]

The Digital Imaging and Communication in Medicine (DICOM) Standard is used globally to store, exchange, and transmit medical images. The DICOM Standard incorporates protocols for imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and radiation therapy.[35] DICOM includes standards for image exchange (e.g., via portable media such as DVDs), image compression, 3-D visualization, image presentation, and results reporting.[36]

Medical imaging techniques produce very large amounts of data, especially from CT, MRI and PET modalities. As a result, storage and communications of electronic image data are prohibitive without the use of compression. JPEG 2000 is the state-of-the-art image compression DICOM standard for storage and transmission of medical images. The cost and feasibility of accessing large image data sets over low or various bandwidths are further addressed by use of another DICOM standard, called JPIP, to enable efficient streaming of the JPEG 2000 compressed image data.

There has been growing trend to migrate from PACS to a Cloud Based RIS. A recent article by Applied Radiology said, As the digital-imaging realm is embraced across the healthcare enterprise, the swift transition from terabytes to petabytes of data has put radiology on the brink of information overload. Cloud computing offers the imaging department of the future the tools to manage data much more intelligently.[37]

Medical imaging has become a major tool in clinical trials since it enables rapid diagnosis with visualization and quantitative assessment.

A typical clinical trial goes through multiple phases and can take up to eight years. Clinical endpoints or outcomes are used to determine whether the therapy is safe and effective. Once a patient reaches the endpoint, he or she is generally excluded from further experimental interaction. Trials that rely solely on clinical endpoints are very costly as they have long durations and tend to need large numbers of patients.

In contrast to clinical endpoints, surrogate endpoints have been shown to cut down the time required to confirm whether a drug has clinical benefits. Imaging biomarkers (a characteristic that is objectively measured by an imaging technique, which is used as an indicator of pharmacological response to a therapy) and surrogate endpoints have shown to facilitate the use of small group sizes, obtaining quick results with good statistical power.[38]

Imaging is able to reveal subtle change that is indicative of the progression of therapy that may be missed out by more subjective, traditional approaches. Statistical bias is reduced as the findings are evaluated without any direct patient contact.

Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are routinely used in oncology and neuroscience areas,.[39][40][41][42] For example, measurement of tumour shrinkage is a commonly used surrogate endpoint in solid tumour response evaluation. This allows for faster and more objective assessment of the effects of anticancer drugs. In Alzheimers disease, MRI scans of the entire brain can accurately assess the rate of hippocampal atrophy, while PET scans can measure the brains metabolic activity by measuring regional glucose metabolism,[38] and beta-amyloid plaques using tracers such as Pittsburgh compound B (PiB). Historically less use has been made of quantitative medical imaging in other areas of drug development although interest is growing.[43]

An imaging-based trial will usually be made up of three components:

Lead is the main material used for radiographic shielding against scattered X-rays.

In magnetic resonance imaging, there is MRI RF shielding as well as magnetic shielding to prevent external disturbance of image quality.

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iPSCells Represent a Superior Approach

iPS cell-derived cardiomyocyte patch demonstrates spontaneous and synchronized contractions after 4 days in culture.

One of the greatest promises of human stem cells is to transform these early-stage cells into treatments for devastating diseases. Stem cells can potentially be used to repair damaged human tissues and to bioengineer transplantable human organs using various technologies, such as 3D printing. Using stem cells derived from another person (allogeneic transplantation) or from the patient (autologous transplantation), research efforts are underway to develop new therapies for historically difficult to treat conditions. In the past, adult stem and progenitor cells were used, but the differentiation of these cell types has proven to be difficult to control. Initial clinical trials using induced pluripotent stem (iPS) cells indicate that they are far superior for cellular therapy applications because they are better suited to scientific manipulation.

CDIs iPS cell-derived iCell and MyCell products are integral to the development of a range ofcell therapyapplications. A study using iCell Cardiomyocytesas part of a cardiac patch designed to treat heart failure is now underway. This tissue-engineered implantable patch mayemerge as apotential myocardial regeneration treatment.

Another study done with iPS cell-derived cells and kidney structures has marked an important first step towards regenerating, and eventually transplanting, a functioning human organ. In this work, iCell Endothelial Cellswere used to help to recapitulatethe blood supply of a laboratory-generated kidney scaffold. This type of outcome will be crucial for circulation and nutrient distribution in any rebuilt organ.

iCell Endothelial Cells revascularize kidney tissue. (Data courtesy of Dr. Jason Wertheim, Northwestern University)

CDI and its partners are leveraging iPS cell-derived human retinal pigment epithelial (RPE) cells to develop and manufacture autologous treatments for dry age-related macular degeneration (AMD). The mature RPE cells will be derivedfrom the patients own blood cells using CDIs MyCell process. Ifapproved by the FDA, this autologous cellular therapy wouldbe one of the first of its kind in the U.S.

Learn more about the technologybehind the development of these iPScell-derived cellular therapies.

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Cellular Therapy - The World Leader in Stem Cell Technology

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Microneedling has quickly become one of the most popular skin rejuvenation treatments. If youre considering trying it, here is what you need to know.

Microneedling, also called collagen-induction therapy, uses small needles that pierce the outermost layer of skin to create tiny microchannels. These microchannels help stimulate the production of collagen and elastin within the skin. They also promote new capillaries.

This can lead to an improved skin texture, reduction of acne or other scarring and help with discoloration, such as brown spots caused by sun damage. Microneedling may be combined with platelet-rich plasma, stem cells, or pure hyaluronic acid to enhance results further.

Microneedling can also be used on the scalp to help stimulate hair rejuvenation.

Prior to your first microneedling session, you will be asked to avoid sun exposure for at least 24 hours. Some doctors will tell you to avoid blood-thinning medications and herbal supplements like aspirin, ibuprofen and St. Johns wort to reduce bruising.

Each microneedling session takes about 20 to 30 minutes. First, your face will be cleansed and a numbing cream will be applied. Multiple treatment sessions, spaced a few weeks apart, are recommended. Most doctors recommend three to six treatments but many will notice an improvement in the tone and texture of their skin after just one treatment.

Immediately after your microneedling session, you will likely notice some redness that can last for several days. In my practice, we recommend that patients do not touch their face for at least four hours after treatment and do not apply anything to the face for 24 hours. It is crucial to avoid sun exposure for three days after the procedure.

You should avoid strenuous activity and exercise for the first 12 hours after treatment to prevent redness and bruising. For the first three days after treatment, you should use a gentle non-foaming cleanser, a barrier repair moisturizer, and a physical SPF. If swelling or bruising are a concern, you can take arnica supplements both before and after treatment to help minimize these side effects.

Once any redness or swelling diminishes, you should notice an immediate improvement in the way your skin looks and feels. Over the next several weeks, your skins appearance should continue to improve.

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A new therapy changes the balance of osteoblasts (pictured here) and fat cells in the bone marrow, leading to stronger bones.

Science Picture Co/Science Source

By Emma YasinskiSep. 5, 2017 , 2:59 PM

A drug that can reverse diabetes and obesity in mice may have an unexpected benefit: strengthening bones. Experiments with a compound called TNP (2,4,6-trinitrophenol, which is also known as picric acid), which researchers often use to study obesity and diabetes, show that in mice the therapy can promote the formation of new bone. Thats in contrast to many diabetes drugs currently in wide use that leave patients bones weaker. If TNP has similar effects in humans, it may even be able to stimulate bone growth after fractures or prevent bone loss due to aging or disuse.

As more and more patients successfully manage diabetes with drugs that increase their insulin sensitivity, doctors and researchers have observed a serious problem: Thedrugs seem to decrease the activity of cells that produce bone, leaving patients prone to fractures and osteoporosis.

There are millions and millions of people that have osteoporosis [with or without diabetes], and it's not something we can cure, says Sean Morrison, a stem cell researcher at University of Texas Southwestern in Dallas. We need new agents that promote bone formation.

Morrison and his colleagues have shown that a high-fat diet causes mice to develop bones that contain more fat and less bone. The diet increased the levels of leptina hormone produced by fat cells that usually signals satiety in the brainin the bone marrow, which promoted the development of fat cells instead of bone cells. That suggests that nutrition has a direct effect on the balance of bone and fat in the bone marrow.

After reading Morrisons work, Siddaraju Boregowda, a stem cell researcher at the Scripps Research Institute in Jupiter, Florida, was reminded of genetically altered mice that dont gain body fat or develop diabetes, even when fed high-fat diets. He and his boss, stem cell researcher Donald Phinney, wondered whetherthose mice were also protected from the fattening of the bone marrow that accompanies a high-fat diet.

They contacted Anutosh Chakraborty, a molecular biologist who was studying such mice down the hall at Scripps at the time. The animals lack the gene for an enzyme called inositol hexakisphosphate kinase 1 (IP6K1), which is known to play a role in fat accumulation and insulin sensitivity. The scientists suspected that the lost enzyme might affect the animals' mesenchymal stem cells (MSCs)stem cells found in the bone marrow that are capable of developing into both thebone cells and fat cells that make up our skeletons. If too many fat cells develop, they take the place of bone cells, weakening the bone.

The researchers fed genetically altered and normal mice a high-fat diet for 8weeks. Not only did the genetically altered mice develop fewer fat cells than their normal counterparts, but their production of bone cells was higher than that of the normal mice, the team reported last month in Stem Cells.

The scientists then set out to see whetherthey could use a drug to achieve the same effect in normal mice. For 8weeks, they fed normal mice a high-fat diet and gave them daily injections of either TNP, a well-known IP6K1 inhibitor, or a placebo. When they analyzed the animals bones and marrow, they found that mice that had received TNP had significantly more bone cells, fewer fat cells, and greater overall bone area. The IP6K1 inhibitor apparently protected the mice from the detrimental effects of the high-fat diet.

The study provided thesurprising result that one new therapy currently being explored to lower insulin resistance promotes, rather than decreases, the formation of bone in mice, says DarwinProckop,a stem cell researcher at Texas A&M College of Medicine in Temple, who was not involved in the work.

The researchers still need to figure out how to deliver TNPs effects only to MSCs, instead of the entire body, given that it sometimes blocks other enzymes along with IP6K1. Inhibition of IP6K1 is a promising target for patients with both diabetes and obesity, Boregowda says. He says he and his colleagues are now enthusiastic about testing their findings in a wide range of bone-related diseases and disorders. It might even help heal broken bones, he speculates.

Phinney, on the other hand, is aiming even higher. He wonders whetherthe therapy could also be useful for space travel, because bones are especially vulnerable to deterioration in zero gravity. Its a whole new field of science and drug discovery.

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Every mom anticipates her childs first day at kindergarten.

For Jessica Pequeno, that kind of milestone is something this mom is only now ready to imagine.

The last time the Napa Valley Register wrote about the Pequeno family, it was October 2015. Their then 22month-old toddler Xavier was about to begin the fight of his life against an immune deficiency disorder so rare it had no name.

Today, there is good news about Xavier and his family.

The now 4-year-old completed a grueling, yet successful stem cell transplant, just started his second year of preschool and is making progress with his health, said his mother. Come this time next year, shell be enrolling him in kindergarten.

Every day is different. We still deal with so many unknowns, she said. But, Hes doing so much better than anybody would have ever expected.

Just getting to this point was a long road.

Two years ago, the Pequenos told their story in hopes of finding a bone marrow transplant match for their son. Doctors originally told them there was no match within the family. Fortunately, after a second set of tests, the Pequenos middle son, Higinio Pequeno IV, was identified as a partial match.

That news was awesome, said Jessica Pequeno.

The family prepared for the transplant to take place in June 2015, but a stubborn infection put those plans on hold. By December, his health care team at the University of California at San Francisco wouldnt even give us odds as his percentage of survival because they didnt know, she said.

They finally had a name for his disease IKBa gain of function mutation with ectodermal dysplasia but there were too many unknowns.

Pequeno said she realized the stem cell transplant was a kind of a now-or-never situation.

We just kept saying, We just have to keep doing this. Giving up wasnt an option.

On Dec. 1, 2015, Xavier was admitted to the hospital for the transplant. The process began with eight days of chemotherapy followed by the stem cell transplant.

Putting a line in his femoral artery, blood was collected from Higinio, then 10. Then a machine separated the stem cells from the blood. Higinios stem cells were then given to Xavier. The stem cells were put into a vein, much like a blood transfusion. The stem cells are then meant to travel to the bone marrow, engraft, and hopefully begin making new, normal blood cells.

On the day of the transplant, the whole Pequeno family, including her husband Higinio, son Higinio and daughter Maya and Jessica Pequenos mom were there. Seeing those potentially life-saving cells go into her son was very emotional, said Jessica Pequeno.

We all cried, she said. It was really scary, but you cant stop. You have to keep going.

During the procedure, Xavier was awake, she said. But the side-effects of the chemotherapy were starting to set in. His hair was falling out, and he had stopped eating and drinking because his mouth sores were so bad and painful, she said. He was on morphine for the pain.

The waiting began. Would the stem cell transplant be a success?

The family was told that Xavier would likely spend many months in the hospital. We planned to be separated as a family for at least six months, said Pequeno. We just expected it to be really hard.

She spent her nights in the room with her son, sleeping on a blow-up twin mattress. The rest of her family went back to Napa. Because Jessica was unable to work and her husband couldnt work because he needed to have knee surgery, the family had moved in with Jessicas mother.

Meanwhile, doctors continued to check Xaviers blood to see if his body was responding to the stem cell transplant.

Every day Id ask, Where are we at? his mother said.

And then, one day in early January, the doctors came to see Xavier, and they said, We have good news.

The transplant was starting to work and the new cells were starting to grow, she said.

I cried, said Pequeno. It happened so much faster than what they had expected.

By the end of January, Xavier was well enough to go home to Napa.

It was scary to come home and super exciting, she said.

Back at home, a new routine was created. Xavier was still taking 25 different medications, some multiple times per day. He had a gastrostomy or G tube for feeding the nutritional liquid he eats and a central line a thin, flexible tube used to give medicines, fluids, nutrients, or blood products over a long period of time.

Honestly I dont remember a lot of it. It becomes a big blur, said Pequeno.

The family continued to visit UCSF at least once a week for blood counts and other checks. There were more ups and downs. Infections and illnesses caused him to be hospitalized for days at a time in February, May and June. His central line got infected. He got shingles.

His immune system was still really weak, said Pequeno.

But he kept bouncing back.

Just two weeks ago, doctors finally removed his central line.

It was a huge step, she said.

Challenges remain. Before the stem cell transplant, Xavier had about 5 to 10 percent of a normal immune system. Now he has about 60 to 70 percent, doctors said.

Were starting to learn hes really prone to sinus and respiratory infections, and viruses, said Pequeno. His body just doesnt fight like everyone elses.

Other habits are harder to change.

Before Xavier went to preschool, Pequeno and her family were able to carefully control his exposure to germs.

When he was able to go to preschool, I wasnt in control of those environments anymore. Its really hard. It gets easier, but it takes a while to learn how to kind of let go, she said.

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Today, Xavier takes only six medications a day and can receive infusions of antibodies at home. Visits to UCSF have been cut back to once every four to five weeks.

Developmentally, Xavier is doing well, she said.

He has some hearing loss, which we continue to monitor. Its hard to say if its a side effect of chemo or other drugs. Right now it doesnt affect his speech. He also has skin, hair and teeth health issues to manage.

Xavier doesnt complain at lot, said Pequeno.

Hes always handled everything so well. When he suffered, He would get quiet. Even now when hes not feeling good, instead of crying like many small children would, Xavier is quiet.

Financially, its hard because Im still not able to work, she said.

Xaviers medical care is provided by Partnership HealthPlan/Medi-Cal and California Childrens Services. Her husband went back to work. Pequeno is taking classes at Napa Valley College while her son is in preschool.

I want to be a nurse but I want to go into pediatrics I want to teach parents how to advocate for their kids.

One of the most significant changes for Pequeno was becoming more confident in working with health care providers regarding her sons care.

Nobody could hand me a book when this started (that said) these are the things you need to know and questions to ask. No one told me I was the captain of his team. Her confidence grew. You have to get comfortable in that role.

The past several years have left a lasting imprint on the whole family, she said. Signs of post-traumatic stress have been seen in all family members. Learning coping skills and how to manage stress is important.

Especially for their son Higinio, said his mother. Its not easy for young boy to come to terms with what his brother went through and his own unique contribution.

I dont think any 10-year-old is capable of understanding the weight that carries, she said.

The struggles havent ended, said Pequeno.

Weve just learned to manage them and adjust and deal with the financial part. We juggle. You learn how to change your priorities.

Its easy to say her son looks healthy, said Pequeno, but thats also frustrating because it takes so much work to get him to continue to look like that.

It definitely takes a toll and lot of work and sacrifice to keep him where hes at, she said.

And Xaviers condition isnt going away, she noted. This is something we will manage for the rest of his life one way or the other.

People say, Oh youre so strong. But I think that as a mom, you just do it, said Pequeno. You pull the strength from somewhere. Because you dont give up on your kids.

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Scanning electron micrograph of blood cells. From left to right: human erythrocyte, thrombocyte (platelet), leukocyte. Credit: public domain

For more than a century, physicians have anecdotally noted that patients with an underactive thyroidoften caused by iodine deficiencytended to also have anemia. But the link between thyroid hormone and red blood cell production has remained elusive. That is, until two postdoctoral researchers in the lab of Whitehead Institute Founding Member Harvey Lodish, Xiaofei Gao and Hsiang-Ying "Sherry" Lee, decided to investigate.

During the development of red blood cells, specialized bone marrow stem cells mature through several stages until they finally turn on the genes for hemoglobin and other red blood cell proteins and become mature red blood cells. In order to simulate this process in the lab, researchers have previously found that culturing blood cell progenitors in serum helps them turn on all of the proper proteins to take the final step and become a red blood cell.

Gao and Lee, now Principal Investigators at Westlake Institute for Advanced Study and Peking University, respectively, wondered if something in the serum was key to flipping the switch to becoming a mature red blood cell. To narrow down which of the molecules in the serum is the trigger, Gao and Lee ran the serum through a standard laboratory filter that many of us use everyday for our tap water: charcoal.

Long known for sucking odors out of the air and flavors from water, charcoal attracts and retains hydrophobic (water repellent) molecules. Gao and Lee noticed that once filtered, the serum no longer supported red blood cell production; they deduced that one of the hydrophobic molecules trapped by charcoal is the key to the final step of red blood cell maturation. Gao and Lee determined that when just the thyroid hormone thyroxin is added back to the serum, the red blood cell progenitors once again start down the path to maturation. Thyroid hormone's role is so important in stimulating red blood cell maturation, they discovered, that if it is added at an earlier stage of development, red blood cells short-circuit their usual developmental processes and begin turning into mature red blood cells.

Gao and Lee then teased apart the mechanism behind thyroid hormone's effect on red blood cell maturation. They pinpointed the specific type of receptor inside maturing red blood cells to which thyroid hormone binds. From there, they identified a protein that is necessary for thyroid hormone stimulation and that acts as a regulator of the final step of red blood cell production.

With this better understanding of the connection between thyroid hormone and red blood cell maturation, scientists may be able to identify new therapies that trigger red blood cells maturation in patients with specific types of anemia, including those with an underactive thyroid.

The study is published in PNAS.

Explore further: Low thyroid hormone before birth alters growth and development of fetal pancreas

More information: Xiaofei Gao et al. Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1711058114

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Mystery solved: How thyroid hormone prods red blood cell production - Medical Xpress

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At just four-years-old, Erica Honoways son has gone through more than most people will experience in a lifetime.

In February 2016, the family received devastating news, her son Lincoln had been diagnosed with bone marrow failure. He was just three years old at the time.

Lincoln needed a bone marrow transplant, and doctors were only able to find two matches in the entire world. The first donor fell through, so Lincoln was left with only one option.

It was terrifying. We didnt know what we were dealing with, Honoway said. We didnt know what the chances were they would find a match for him. Even if they did, we didnt know if he would make it through the transplant, so it was the scariest experience of our lives.

After the blood transfusions, chemotherapy, radiation and bone marrow transplant, Lincoln is now a happy and active four year old, all thanks to an unknown hero.

This person has just been our angel, Honoway said. We love her and we dont even know her. We say her We have a feeling its a woman but we dont know anything about this person. We dont know where in the world they live, we dont know if its a man or a woman, we dont know anything. But all we know is that they are our hero.

Honoway added that they must wait a minimum of two years before they can meet the donor.

Lincolns successful transplant was the reason Honoway and her family were supporting the University of Reginas Get Swabbed event on Monday, to encourage students between the ages of 17 and 35 to get their cheeks swabbed and enter a national stem call database.

I heard about Erica and Lincoln and I just thought it was amazing how someone just saved his life, and she doesnt even know who he is or who she is, I just think its amazing, U of R Stem Cell Club president Sylvia Okonofua said. I felt like if I take up this initiative and actually run drives where people [can get] on the stem cell registry, [it can] help save a life someday.

Getting students involved and realizing their impact of their involvement through something like this was one of the main goals, U of R student engagement co-ordinator Doug OBrien said. Another goal of having todays Get Swabbed initiative was obviously to support the stem cell database for Canada and through the One Match program.

Approximately 80 students took part in Mondays Get Swabbed event, and organizers are hoping to increase that number for the next event on Sept. 14.

Its a simple way to help save a life.

I hope people realize that they have the opportunity to save someones life, imagine what that would feel like, Honoway said. Youd get to know forever that you saved another humans life. Its pretty special.

2017Global News, a division of Corus Entertainment Inc.

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TEL AVIV, Israel, Sept. 5, 2017 /PRNewswire/ -- Cellect Biotechnology Ltd. (NASDAQ: APOP), a developer of stem cells selection technology, announced today that theU.S. Food and Drug Administration(FDA) has granted orphan drug designation for Cellect's ApoGraft for the prevention of acute and chronic graft versus host disease(GvHD) in transplant patients.

GvHD is a transplant associated disease representing an outcome of two immune systems crashing into each other. In many transplantations from donors, and especially in Bone Marrow Transplantations (BMT), the transplanted immune mature cells (as opposed to stem cells) attack the host (patient receiving the transplant) and create severe morbidity and in many cases even death.

This disease happens as a result of current practices being unable to separate the GvHD causing cells from the much needed stem cells.Cellect's ApoGraft was designed to eliminate immune responses in any transplantation of foreign cells and tissues.

Cellect's AppoGraft technology can be utilized already today to help thousands of development and research centers globally engaged in adult stem cells based therapeutics by providing them with a simplified and cost efficient enriched stem cells for use as a raw material for a wide range of stem cells based therapeutics R&D. Before Cellect's ApoGraft, such procedures were extremely complex, inefficient and required substantial resources in both cost, time and infrastructure requirements. ApoGraft can now be used to significantly advance the use of stem cells across multiple therapeutics indications as well as research and biobanking purposes.

The FDA Orphan Drug Act provides incentives for companies to develop products for rare diseases affecting fewer than 200,000 people inthe United States. Incentives may include tax credits related to clinical trial expenses, an exemption from theFDAuser fee, FDAassistance in clinical trial design and potential market exclusivity for seven years following approval.

About Cellect Biotechnology Ltd.

Cellect Biotechnology (NASDAQ: "APOP", "APOPW") has developed a breakthrough technology for the selection of stem cells from any given tissue that aims to improve a variety of stem cell applications.

The Company's technology is expected to provide pharma companies, medical research centers and hospitals with the tools to rapidly isolate stem cells in quantity and quality that will allow stem cell related treatments and procedures. Cellect's technology is applicable to a wide variety of stem cell related treatments in regenerative medicine and that current clinical trials are aimed at the cancer treatment of bone marrow transplantations.

Forward Looking Statements

This press release contains forward-looking statements about the Company's expectations, beliefs and intentions. Forward-looking statements can be identified by the use of forward-looking words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. For example, forward-looking statements are used in this press release when we discuss the Company's pathway for commercialization of its technology. These forward-looking statements and their implications are based on the current expectations of the management of the Company only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. In addition, historical results or conclusions from scientific research and clinical studies do not guarantee that future results would suggest similar conclusions or that historical results referred to herein would be interpreted similarly in light of additional research or otherwise. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; we may encounter delays or obstacles in launching and/or successfully completing our clinical trials; our products may not be approved by regulatory agencies, our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; we may be unable to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties may develop with our process; our products may wind up being more expensive than we anticipate; results in the laboratory may not translate to equally good results in real clinical settings; results of preclinical studies may not correlate with the results of human clinical trials; our patents may not be sufficient; our products may harm recipients; changes in legislation; inability to timely develop and introduce new technologies, products and applications, which could cause the actual results or performance of the Company to differ materially from those contemplated in such forward-looking statements. Any forward-looking statement in this press release speaks only as of the date of this press release. The Company undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. More detailed information about the risks and uncertainties affecting the Company is contained under the heading "Risk Factors" in Cellect Biotechnology Ltd.'s Annual Report on Form 20-F for the fiscal year ended December 31, 2016 filed with the U.S. Securities and Exchange Commission, or SEC, which is available on the SEC's website, http://www.sec.gov. and in the Company's period filings with the SEC and the Tel-Aviv Stock Exchange.

ContactCellect Biotechnology Ltd. Eyal Leibovitz, Chief Financial Officerwww.cellect.co+972-9-974-1444

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Kathmandu, September 4

Civil Hospital is launching haploidentical stem cell transplant within a few months.

Its a treatment process for patients with blood-related cancers and certain blood disorders.

Patients who need a stem cell transplant and cant find a donor who matches their tissue type will benefit from the transplant. Haploidentical transplant is a modified form of stem cell transplant in which a healthy first degree relative a parent, or sibling can often serve as a donor.

When no matched donor is available, half-matched related (haploidentical) donors are safely used in stem cell transplantation, informed Dr Bishesh Poudyal, associate professor and chief of Clinical Hematology and Bone Marrow Transplant Unit at the hospital.

The cost of the transplant will be around 12 to 15 lakh rupees. People suffering from blood cancer, aplastic anaemia, sickle cell anaemia and thalassemia will benefit from the transplant.

The hospital has been performing allogeneic and autotransplant stem cell transplant where only siblings can be donors.

Nine patients had undergone autotransplant and one had undergone allogeneic stem cell transplant in the hospital after it started bone marrow transplant in the hospital in 2016.

A version of this article appears in print on September 05, 2017 of The Himalayan Times.

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The US Food and Drug Administration (FDA) intendsto investigate the use of unproven stem cell therapies being offered in the country'sclinics.

Tighter enforcement from the FDA comes as an inspection at StemImmune Inc based in San Diego, California, revealed the use of potentially dangerous treatments administered to vulnerable cancer patients.

Only a small number of stem cell treatments are currentlyFDA approved, including use of bone marrow transplants in cancer patients and cord blood for specific blood-related disorders.However stem cell treatments using only the patient's own cells are not subject to the same level of regulation as drugs if the cells are only 'minimally manipulated'.

FDA commissioner Dr Scott Gottlieb said in a statement:'The FDA will not allow deceitful actors to take advantage of vulnerable patients by purporting to have treatments or cures for serious diseases without any proof that they actually work. I especially wont allow cases such as this one to go unchallenged, where we have good medical reasons to believe these purported treatments can actually harm patients and make their conditions worse.'

Five vials,each containing 100 doses of the live Vaccinia Virus Vaccine, were seized from StemImmune Incby US marshals on25August 2017.

The vaccine, which is usedagainst smallpox, and is not commercially available was combined with stem cells derived from body fat to create an unapprovedtherapy. The concoction was injected directly into tumours of cancer patients at California Stem Cell Treatment Centres in Rancho Mirage and Beverly Hills.

The effects of the vaccine in immunocompromised cancer patients have the possibility to cause severe complications such as inflammation and swelling of the heart and surrounding tissues.

In a separate case, awarning letter was also sent to chief scientific officerKristin Comellaat US Stem Cell Clinic in Sunrise, Florida, after three patients with macular degeneration were blinded following the use of unapproved stem cell injections into their eyes, in a sponsored study (see BioNews 893). The letter lists a number of non-compliance to procedures and 'significant deviations' to current good manufacturing practice and good tissue practice.

'Our actions today should also be a warning to others who may be doing similar harm, we will take action to ensure Americans are not put at unnecessary risk,' Dr Gottlieb commented. 'I also urge health care providers, patients and consumers to report these kinds of activities or any adverse events associated with these unproven treatments to the agency through MedWatch a safety reporting programme.'

Professionals in the field blame the past lack of FDA attention for the widespread problem and are calling for stringent regulation. ProfessorLeigh Turner, fromthe Centre for Bioethics at the University of Minnesota, told CNN: 'This is a space where the FDA could have taken action four or five years ago as far as making this a policy priority.'

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The bone marrow transplant unit of this hospital was inaugurated in February 2014. The unit was the first of its kind in Cuttack and the government announced that this surgery will be conducted free of cost. Read the full report here.

SCB succeeds in conducting 50 such surgeries free of cost in the past 3 years.

"The successful completion of the surgery is a new milestone for the country and the state." says Rabindra Kumar Jena, head of clinical haematology at SCB. Haematologists revealed that this transplant is conducted when a persons bone marrow becomes weak due to chronic infections, diseases or cancer and does not function properly. In this procedure, new blood stem cells are transplanted which travel to the bone marrow, new blood cells are produced and the growth of a new marrow is promoted.

"A bone marrow transplant replaces your damaged stem cells with the healthy ones. This helps your body make enough white blood cells, platelets or red blood cells to avoid infections, bleeding disorders or anaemia," says haematologist Sudha Sethy.

"The patient is under observation, as the post-operative period is generally critical. She needs to be kept in a sanitised isolation room to avoid infection." Dr Jena informed. He also said that SCB is the only government hospital in the country which provides good quality facilities for bone marrow transplant surgery free of cost. Though the entire process costs two lakhs in a government hospital and over ten lakhs in private hospitals, SCB succeeds in conducting 50 such surgeries free of cost in the past 3 years.

The team of haematologists who succeeded in achieving this goal were R.K. Jena, Sudha Sethy, Rajeeb Nayak, Manmohan Biswal, S.B. Rout and C.R. Kar. "Of all the few 50 patients, who have undergone transplants here, 46 people are living a healthy and normal life. There had been three deaths - two due to infection after the transplant and another after 178 days of the transplant due to brain stroke, which was not in anyway related to the disease." said Jena.

The bone marrow transplant unit of this hospital was inaugurated in February 2014. The unit was the first of its kind in Cuttack and the government announced that this surgery will be conducted free of cost. Odisha State Treatment Fund is funding Nayaks surgery. Another haematologist at the department revealed, "The eldest person to have undergone a bone marrow transplant from the entire continents of Asia and Europe is Zabar Kahan, 74, who was a patient here. We have also conducted the transplant on five patients at age of above 65 years, which is the first of its kind in entire India, Asia and Europe."

He added "We are all set to take more complicated cancer patients for bone marrow transplants. Besides, we are also expanding the unit to accommodate more patients suffering from thalassemia, sickle cell disease and cancer."

SCB adds that at least 3000 people of the state need this surgery.

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Drugs developed to treat heart and blood vessel problems could be used to treat leukaemia

Drugs developed to treat heart and blood vessel problems could be used in combination with chemotherapy to treat an aggressive form of adult leukaemia.

Researchers at the Francis Crick Institute, Kings College London and Barts Cancer Institute discovered that acute myeloid leukaemia (AML) causes bone marrow to leak blood, preventing chemotherapy from being delivered properly.

Drugs that reversed bone marrow leakiness boosted the effect of chemotherapy in mice and human tissue, providing a possible new combination therapy for AML patients.

To study how AML affects bone marrow, the researchers injected mice with bone marrow from AML patients. Later, they compared their bone marrow with healthy mice using a technique called intravital microscopy that allows you to see biological processes in live animals. They found that pre-loaded fluorescent dyes leaked out of the bone marrow blood vessels in AML mice, but not healthy mice.

Next, the team tried to understand what caused the bone marrow in AML mice to become leaky by studying molecular changes in the cells lining the blood vessels. They found that they were oxygen-starved compared to healthy mice, likely because AML cells use up a lot of oxygen in the surrounding tissue. In response to a reduction in oxygen, there was an increase in nitric oxide (NO) production a molecule that usually alerts the body to areas of low oxygen.

As NO is a muscle relaxant, the team suspected that it might be causing bone marrow leakiness by loosening the tight seams between cells, allowing blood to escape through the gaps. By blocking the production of NO using drugs, the team were able to restore bone marrow blood vessels in AML mice, preventing blood from leaking out. Mice given NO blockers in combination with chemotherapy had much slower leukaemia progression and stayed in remission much longer than mice given chemotherapy alone.

When the vessels are leaky, bone marrow blood flow becomes irregular and leukaemia cells can easily find places to hide and escape chemotherapy drugs, said researcher Dr Diana Passaro. Leaky vessels also prevent oxygen reaching parts of the bone marrow, which contributes to more NO production and leakiness.

By restoring normal blood flow with NO blockers, we ensure that chemotherapy actually reaches the leukaemia cells, so that therapy works properly, she added.

In addition to ensuring that chemotherapy drugs reach their targets, the team also found that NO blockers boosted the number of stem cells in the bone marrow. This may also improve treatment outcomes by helping healthy cells to out-compete cancerous cells.

The team also found that bone marrow biopsies from AML patients had higher NO levels than those from healthy donors, and failure to reduce NO levels was associated with chemotherapy failure.

Our findings suggest that it might be possible to predict how well people with AML will respond to chemotherapy, said Dr Dominique Bonnet, senior author of the paper and Group Leader at the Francis Crick Institute.

Weve uncovered a biological marker for this type of leukaemia as well as a possible drug target. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, said Dr Passaro. As the drugs are already in clinical trials for other conditions, it is hoped that they could be given the green light for AML patients in the future.

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Irish researcher Prof Daniel Kelly has secured 150,000 in funding to develop a novel implant for treating cartilage damage.

As a recipient of one of the European Research Councils Proof of Concept grants, Prof Daniel Kelly will now spend the next 18 months developing his 3D-printed project entitled Anchor.

Using the 150,000, Kelly will look to develop and commercialise his new medicinal product for cartilage regeneration, employing a postdoctoral researcher to help.

Those active in many sports would be familiar with cartilage damage as a result of injury, of which many cases occur in the knee joint. If left untreated, it can lead to difficulties such as osteoarthritis (OA).

OA can be a debilitating condition, with 80pc of those over the age of 60 experiencing limitations in movement and 25pc saying they cannot perform their major daily activities, according to the World Health Organisation.

Kellys product uses 3D-printed, biodegradable polymer components to make a scaffold, which acts as a template to guide the growth of new tissue by recruiting endogenous bone marrow derived from stem cells.

This, Kelly believes, gives it a competitive edge over similar implants, as standard ones are designed with a finite lifespan, making them unsuitable for younger patients with OA.

Kelly, a principal investigator at AMBER the Trinity College Dublin materials science research centre explained why it could be a major breakthrough for other conditions, such as arthritis.

Our 3D-printed polymer posts will anchor the implant into the bone and will be porous to stimulate the migration of stem cells from the bone marrow into the body of the scaffold, he said.

While various scaffolds like this have been available for some time, they have had limited success, partly because scaffolds need to be anchored securely due to the high forces experienced within the joint. Our 3D-printed posts overcome this problem.

Prior to Anchor, Kelly had worked on this technology in previous projects, such as the ERC-funded StemRepair project to develop a range of porous cartilage-derived scaffolds, and JointPrint.

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Chemical changes in the eye that can lead to blindness have been identified by scientists, a conference will hear tomorrow (Tuesday 5 September).

Their findings aid understanding of a genetic condition that causes sight loss for one in 3,000 people in the UK.

They will be presented at the Eye Development and Degeneration 2017 conference in Edinburgh.

Eye condition

Scientists examined how changes in a gene known as RPGR damage eye cells to cause a disorder known as X-linked retinitis pigmentosa.

The condition is incurable and affects night and peripheral vision before gradually causing blindness in middle age.

Skin samples

A team led by Edinburgh researchers took skin samples from two patients and transformed stem cells which can change into any cell type into light-sensing eye cells known as photoreceptors.

They compared these with cells from healthy relatives of the patients.

Photoreceptors which decay in retinitis pigmentosa patients differed in their fundamental structure when compared with those from family members.

Key molecules

Follow-up studies in mice identified key molecules that interact with RPGR to maintain the structure of photoreceptors.

When RPGR is flawed, the structure is compromised and photoreceptors cannot function correctly, leading to sight loss.

The study is published in the journal Nature Communications and was carried out at the University of Edinburgh's Medical Research Council Centre for Regenerative Medicine.

It was funded by the Wellcome Trust and the charity Retinitis Pigmentosa Fighting Blindness.

"By furthering our understanding of the RPGR gene and its effects on photoreceptor cells, we hope our findings bring us closer to developing a possible treatment for this devastating disease," says Dr Roly Megaw of the Medical Research Council Institute for Genetics and Molecular Medicine.

Explore further: New trial for blindness rewrites the genetic code

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